G C A T

T A C G
G C A T
genes
Review
Genes and Athletic Performance: The 2023 Update
Ekaterina A. Semenova 1,2 , Elliott C. R. Hall 3 and Ildus I. Ahmetov 4,5,6,7, *

1 Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical
Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia
2 Research Institute of Physical Culture and Sport, Volga Region State University of Physical Culture, Sport and
Tourism, 420138 Kazan, Russia
3 Faculty of Health Sciences and Sport, University of Stirling, Stirling FK9 4UA, UK
4 Laboratory of Genetics of Aging and Longevity, Kazan State Medical University, 420012 Kazan, Russia
5 Sports Genetics Laboratory, St Petersburg Research Institute of Physical Culture, 191040 St. Petersburg, Russia
6 Department of Physical Education, Plekhanov Russian University of Economics, 115093 Moscow, Russia
7 Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 5AF, UK
* Correspondence: [email protected]

Abstract: Phenotypes of athletic performance and exercise capacity are complex traits influenced
by both genetic and environmental factors. This update on the panel of genetic markers (DNA
polymorphisms) associated with athlete status summarises recent advances in sports genomics
research, including findings from candidate gene and genome-wide association (GWAS) studies,
meta-analyses, and findings involving larger-scale initiatives such as the UK Biobank. As of the end
of May 2023, a total of 251 DNA polymorphisms have been associated with athlete status, of which
128 genetic markers were positively associated with athlete status in at least two studies (41 endurance-
related, 45 power-related, and 42 strength-related). The most promising genetic markers include
the AMPD1 rs17602729 C, CDKN1A rs236448 A, HFE rs1799945 G, MYBPC3 rs1052373 G, NFIA-
AS2 rs1572312 C, PPARA rs4253778 G, and PPARGC1A rs8192678 G alleles for endurance; ACTN3
rs1815739 C, AMPD1 rs17602729 C, CDKN1A rs236448 C, CPNE5 rs3213537 G, GALNTL6 rs558129 T,
IGF2 rs680 G, IGSF3 rs699785 A, NOS3 rs2070744 T, and TRHR rs7832552 T alleles for power; and
ACTN3 rs1815739 C, AR ≥21 CAG repeats, LRPPRC rs10186876 A, MMS22L rs9320823 T, PHACTR1
rs6905419 C, and PPARG rs1801282 G alleles for strength. It should be appreciated, however, that
elite performance still cannot be predicted well using only genetic testing.
Citation: Semenova, E.A.; Hall,
E.C.R.; Ahmetov, I.I. Genes and Keywords: sports; genetics; genotype; polymorphism; genomics; physical performance; athletes;
Athletic Performance: The 2023 GWAS; WGS; WES
Update. Genes 2023, 14, 1235.
https://doi.org/10.3390/
genes14061235
1. Introduction
Academic Editor: Paolo Cinelli
Athletic success is influenced by many genetically determined factors, including
Received: 19 May 2023 transcriptomic, biochemical, histological, anthropometric, physiological, and psychological
Revised: 5 June 2023 traits, as well as general health status [1–8]. On average, 66% of the variance in athlete status
Accepted: 7 June 2023
can be explained by genetic factors [9]. The remaining variance is due to environmental
Published: 8 June 2023
factors, such as deliberate practice, nutrition, ergogenic aids, birthplace, the availability of
medical and social support, and even luck (e.g., birthdate) [6,10–12].
Starting in the late 1990s, research began to identify DNA polymorphisms associated
Copyright: © 2023 by the authors.
with predisposition to certain types of sports and exercise-related phenotypes, with initial fo-
Licensee MDPI, Basel, Switzerland. cus on variants of the ACE, ACTN3, AMPD1, PPARA, PPARD, and PPARGC1A genes [13–23].
This article is an open access article Initially, most research was conducted using the candidate gene approach [24–29], which
distributed under the terms and limited progress in the discovery of new genetic markers associated with exercise- and
conditions of the Creative Commons sport-related phenotypes [30]. In addition to the fact that this approach studies only a single
Attribution (CC BY) license (https:// genetic variant in isolation, most candidate gene studies in the field of sports genomics are
creativecommons.org/licenses/by/ limited by sample size. This is a potential source of type I error (false positive findings),
4.0/). underpinning why replication of positive associations in independent cohorts is essential.

Genes 2023, 14, 1235. https://doi.org/10.3390/genes14061235 https://www.mdpi.com/journal/genes

Genes 2023, 14, 1235 2 of 32

Conversely, the genome-wide association approach is considered the most efficient study
design thus far in identifying genetic markers associated with sport-related characteristics.
Indeed, the application of this approach has enabled the discovery of hundreds of single
nucleotide polymorphisms (SNPs) directly or indirectly associated with exercise and sport,
such as height (12,111 SNPs) [31], appendicular lean mass (1059 SNPs) [32], testosterone
levels (855 SNPs) [33], handgrip strength (170 SNPs) [34–36], sarcopenia (78 SNPs) [37],
and brisk walking (70 SNPs) [38].
It is important to consider that the discovery of 12,111 independent genome-wide
(p < 5 × 10−8 ) significant SNPs associated with height (which in combination account for
40% of phenotypic variance) required the study of 5.4 million individuals [31]. Accordingly,
such findings indicate that each DNA locus is likely to explain only a very small proportion
of the reported phenotypic variance (~0.0033%). This also suggests that very large samples
of athletes and non-athletic controls are needed to detect a substantial number of genetic
markers associated with athlete status, with some suggesting those markers be used as
part of talent identification strategies. To date, five genome-wide association (GWAS)
studies [39–43], one whole-genome sequencing (WGS) study [44], and one exome-wide
association (EWAS) study [45] involving athletic cohorts have been conducted. How-
ever, due to their limited sample sizes, these investigations and subsequent replication
studies have resulted in the identification of only 13 genetic markers. Six markers were
associated with endurance athlete status (CDKN1A rs236448 A, GALNTL6 rs558129 C,
NFIA-AS2 rs1572312 C, MYBPC3 rs1052373 G, SIRT1 rs41299232 G, and TRPM2 rs1785440
G alleles) [39,40,42,43,45,46], five with sprinter/strength athlete status (AGRN rs4074992 C,
CDKN1A rs236448 C, CPNE5 rs3213537 G, NUP210 rs2280084 A, and GALNTL6 rs558129
T alleles) [41,45,47,48], and two with reaction time in wrestlers and athlete status in com-
bat/team sports (APC rs518013 A and LRRN3 rs80054135 T alleles, respectively) [44].
To overcome the issue of small samples of elite athletes, the use of genome-wide signif-
icant (p < 5 × 10−8 ) markers of exercise-related phenotypes (correlated with sport-related
traits) discovered in large cohorts of untrained subjects (for example, UK Biobank, FinnGen,
BioBank Japan, etc.) was proposed [49,50]. This approach may significantly decrease the
risk of obtaining false-positive results in the discovery of markers associated with athlete
status, which is recognized as a key limitation of sports genomics studies conducted on
limited sample sizes. Accordingly, the first stage of such an investigation is to list can-
didate genetic markers previously identified in GWAS of exercise-related phenotypes in
non-athletic populations. For example, this may include SNPs associated with phenotypes
of handgrip strength, brisk walking, physical activity, lean mass, forced vital capacity,
haemoglobin, or levels of hormones such as testosterone and IGF1. At the second stage,
microarray analysis (with imputation; covering > 10 million SNPs) is carried out in a group
of athletes to test the hypothesis that favourable alleles of exercise-related phenotypes are
over-represented in those athletes compared to non-athletic controls (Figure 1). This ap-
proach may equally be applied to determine whether favourable alleles could be associated
with direct measures of athletic capability, such as weightlifting performance, running
times, or scores recorded during competitive events. In this case, the significance threshold
for the second stage is set at p < 0.05 (to reduce the likelihood of potentially important
findings being overlooked).
A recent example of such an approach being implemented is the study by Guil-
herme et al. [49], which investigated two correlated phenotypes: brisk walking pace (using
UK Biobank participants) and sprint athlete status (using elite Russian sprinters). Brisk
walkers perform more physical activity, are taller, have reduced adiposity and demonstrate
greater physical performance and strength versus slower walkers, with such traits also
recorded more commonly in sprinters than other athletes of other disciplines. Therefore, it
was hypothesized that the alleles associated with high-speed walking (discovered in un-
trained subjects) would also be over-represented in elite sprinters. Accordingly, 70 genetic
markers of brisk walking were identified from the literature [38], of which 15 SNPs had a
significantly different allele frequency when comparing sprinters with non-athletic con-
 Genes 2023, 14, x FOR PEER REVIEW 3 of 31

Genes 2023, 14, 1235 genetic markers of brisk walking were identified from the literature [38], of which 15 SNPs 3 of 32
had a significantly different allele frequency when comparing sprinters with non-athletic
controls [49]. The same innovative approach later identified 23 SNPs associated with
trols [49]. athlete
strength The samestatus [51] based
innovative on genome-wide
approach significant
later identified markers for
23 SNPs associated handgrip
with strength
strength in a non-athletic population using the UK Biobank [34,35]. Furthermore,
athlete status [51] based on genome-wide significant markers for handgrip strength using ain
apanel of 822 testosterone-related
non-athletic population using theSNPs UKfrom the UK
Biobank Biobank
[34,35]. study [33], five
Furthermore, usingDNA-poly-
a panel of
morphisms
822 associated with
testosterone-related SNPsmuscle fibre
from the UKsize and weightlifting
Biobank performance
study [33], five were identi-
DNA-polymorphisms
fied [50]. with muscle fibre size and weightlifting performance were identified [50].
associated

Figure1.1. Case-control
Figure Case-control study designs in sports genomics.
genomics. In Inthis
thisapproach,
approach,allelic
allelicfrequencies
frequenciesare
are
comparedbetween
compared betweenathletes
athletesand
andcontrols
controls(e.g.,
(e.g.,endurance
endurance athletes
athletes vs.vs. untrained
untrained subjects
subjects or or endur-
endurance
ance
vs. vs. power
power athletes).
athletes). A case-control
A case-control studystudy
maymay be first
be the the first
stepstep followed
followed by abygenotype–phenotype
a genotype–pheno-
type study (e.g., identification of VO2max or weightlifting performance-increasing genotypes among
study (e.g., identification of VO2max or weightlifting performance-increasing genotypes among
athletes). In some cases, studies begin with a genotype–phenotype approach, and the findings are
athletes). In some cases, studies begin with a genotype–phenotype approach, and the findings are
subsequently validated by a case-control study.
subsequently validated by a case-control study.
Another approach that has proven effective in addressing the possibility of false pos-
Another approach that has proven effective in addressing the possibility of false
itive results in sports genomics literature is to perform replication studies in two or more
positive results in sports genomics literature is to perform replication studies in two or
independent athletic cohorts (even with small or moderate sample sizes), followed by a
more independent athletic cohorts (even with small or moderate sample sizes), followed
meta-analysis to quantify the overall effect of a polymorphism on athlete status and/or a
by a meta-analysis to quantify the overall effect of a polymorphism on athlete status
sport- and exercise-related trait [43,52–65]. However, in some cases, replication is not pos-
and/or a sport- and exercise-related trait [43,52–65]. However, in some cases, replication
sible due to the exclusivity of a polymorphism to specific populations based on their geo-
is not possible due to the exclusivity of a polymorphism to specific populations based on
graphic ancestry. For example, the rs671 G/A polymorphism of the aldehyde dehydro-
their geographic ancestry. For example, the rs671 G/A polymorphism of the aldehyde
genase 2 (ALDH2) gene was associated with strength in athletes and non-athletes from the
dehydrogenase 2 (ALDH2) gene was associated with strength in athletes and non-athletes
Japanese population [66–68]. Interestingly, the unfavourable (associated with reduced
from the Japanese population [66–68]. Interestingly, the unfavourable (associated with
strength) rs671 A allele is not present in Europeans or South Asians (frequency 0%), but
reduced strength) rs671 A allele is not present in Europeans or South Asians (frequency
common in Chinese, Japanese, and Vietnamese populations (15–25%). This demonstrates
0%), but common in Chinese, Japanese, and Vietnamese populations (15–25%). This
a notable challenge seeking to replicate genomic findings in larger samples, as increasing
demonstrates a notable challenge seeking to replicate genomic findings in larger samples,
the study sample must also consider the geographic ancestry of participants. This also
as increasing the study sample must also consider the geographic ancestry of participants.
This also highlights the possibility that the genetic determinants of some sport- and exercise-
related phenotypes are restricted to certain populations, demonstrating that increasing
sample size is not as straightforward as simply recruiting participants from multiple
countries and/or continents.
Genes 2023, 14, x FOR PEER REVIEW 4 of 31

highlights the possibility that the genetic determinants of some sport- and exercise-related
Genes 2023, 14, 1235 phenotypes are restricted to certain populations, demonstrating that increasing sample 4 of 32
size is not as straightforward as simply recruiting participants from multiple countries
and/or continents.
As well as the phenotypes of athlete status or competitive performance, several re-
As well as the phenotypes of athlete status or competitive performance, several recent
cent studies have investigated a broader range of traits which may relate directly or indi-
studies have investigated a broader range of traits which may relate directly or indirectly
rectly to athletic capability. These include flexibility, coordination, cardiorespiratory fit-
to athletic capability. These include flexibility, coordination, cardiorespiratory fitness,
ness, spatial ability, stress resilience, mental toughness, fat loss efficiency, and cardiovas-
spatial ability, stress resilience, mental toughness, fat loss efficiency, and cardiovascular and
cular and metabolic responses to training, amongst others [69–84]. For example, combat
metabolic responses to training, amongst others [69–84]. For example, combat athletes are
athletes
more likelyare more likely than
than untrained untrained
subjects subjects
to have to have(COMT
the warrior the warrior
rs4680(COMT rs4680 GG)
GG) genotype [85],
genotype [85], whilst chess players demonstrate an increased
whilst chess players demonstrate an increased frequency of an allele linked to improved frequency of an allele linked
to improved
memory and memory and spatial
spatial ability (KIBRAability (KIBRA
rs17070145 rs17070145
T) [86]. T) [86]. Such
Such discoveries discoveries
demonstrate the
demonstrate the broadening nature of sports genomics
broadening nature of sports genomics in recent times, with focus expanding from in recent times, with focus expand- the
ing from the
traditional traditional
domain domain ofwhat
of investigating investigating
makes elite what makes elite
performers performers
different from the different
general
from the general population into other domains, such as sports
population into other domains, such as sports nutrigenetics [87–100] and areas of sports nutrigenetics [87–100] and
areas of sports medicine, such as genomic variants associated
medicine, such as genomic variants associated with soft-tissue injuries and sports-related with soft-tissue injuries and
sports-related
concussion [101–114]. concussion [101–114].
Technological
Technologicaladvancementadvancementhas haslowered
lowered thethe cost of conducting
cost of conducting genomic
genomic studies, in-
studies,
creasing
increasing accessibility to researchers who wish to investigate the genetic underpinningsof
accessibility to researchers who wish to investigate the genetic underpinnings of
sport
sport and
and exercise phenotypes. Consequently,
exercise phenotypes. Consequently,sports sportsgenomics
genomicsisisa adynamic
dynamic andand continu-
continually
ally developing
developing field,
field, making
making it important
it important totoregularly
regularlyappraise
appraisethethe contribution
contribution of of recent
recent
advances
advancesto tothethe field.
field. Therefore,
Therefore,the theaimaimof ofthethe current
current review
review waswas to to summarise
summarise recent recent
progress
progress in in understanding
understanding the the genetic
genetic determinants
determinantsof ofathlete
athletestatus,
status,andandto to detail
detail novel
novel
DNA
DNApolymorphisms
polymorphismsthat thatmay
mayunderpin
underpindifferences
differences between
between individuals
individuals in intheir
theirathletic
athletic
potential.
potential.
At
Atthe
the time
time of of writing
writing (end
(end of of May
May 2023),
2023), thethe total
total number
number of of DNA
DNA polymorphisms
polymorphisms
associated
associated with withathletic
athletic performance
performance since since the
the first
first discovery
discovery in in 1998
1998 isis 251
251(Figure
(Figure 2). 2). Our
Our
search
searchfor forsports
sportsgenomics
genomicspublications
publications was wasbased
basedon onjournals
journalsindexed
indexedin inmajor
majordatabases
databases
(i.e., PubMed
(i.e., PubMed etc.) etc.) using
usingspecific
specific keykey words
words (e.g.,
(e.g., athletes
athletes ++polymorphism/genotype
polymorphism/genotypeetc.). etc.).
However, not
However, not allall articles
articles were
were included
included in in the
the current
current review
review duedue toto language
language limitations
limitations
(articles written
(articles written in inlanguages
languagesotherotherthanthanEnglish
Englishmust mustcontain
containatatleast
leastabstracts
abstractsininEnglish).
English).
In addition, papers with very
In addition, papers with very small cohort small cohort (less than 25 in athletes/controls), or
athletes/controls), or articlesarticles
with combined
with combined groups groups of of athletes
athletes (for(for example,
example, endurance
endurance ++power powerwithout
withoutseparation)
separation)
were not included.
were included. Abstracts
Abstracts of ofconference
conferenceproceedings
proceedingswere were not
notconsidered.
considered. In In
recognition
recogni-
of the
tion of fact thatthat
the fact many studies
many in the
studies field
in the of sports
field of sports genomics
genomics report associations
report associations basedbasedon
the investigation of small sample sizes, we stipulated that only
on the investigation of small sample sizes, we stipulated that only markers where statisti- markers where statistically
significant
cally associations
significant have been
associations have reported
been reportedin at least
in attwo leaststudies (two case-control
two studies studies
(two case-control
and/or one case-control plus one functional study; including
studies and/or one case-control plus one functional study; including those presented those presented in one article)
in
would be included in the present review.
one article) would be included in the present review.

Figure
Figure2.
2.Sports-related
Sports-relatedgenetic
geneticmarkers
markersdiscovered
discovered between
between 1998
1998 and
and 2023.
2023.

According to these criteria, 128 markers could be associated with athlete status
(41 endurance-related, 45 power-related, and 42 strength-related) from the original 251 iden-
tified in our literature search. The most promising genetic markers (i.e., most replicated
Genes 2023, 14, 1235 5 of 32

and had fewer negative or controversial findings) include AMPD1 rs17602729 C, CDKN1A
rs236448 A, HFE rs1799945 G, MYBPC3 rs1052373 G, NFIA-AS2 rs1572312 C, PPARA
rs4253778 G, and PPARGC1A rs8192678 G alleles for endurance; ACTN3 rs1815739 C,
AMPD1 rs17602729 C, CDKN1A rs236448 C, CPNE5 rs3213537 G, GALNTL6 rs558129 T,
IGF2 rs680 G, IGSF3 rs699785 A, NOS3 rs2070744 T, and TRHR rs7832552 T alleles for
power; and ACTN3 rs1815739 C, AR ≥ 21 CAG repeats, LRPPRC rs10186876 A, MMS22L
rs9320823 T, PHACTR1 rs6905419 C, and PPARG rs1801282 G alleles for strength. This
update on the panel of genetic markers associated with athlete status covers advances in re-
search reported in the past two years (previous online version was published in 2021 [115]).
The current review also lists all known markers associated with endurance, power, or
strength athlete status/performance. This article does not aim to review genetic markers
associated with team (game) and combat sports, markers for which are well described
elsewhere [26,61,116,117].

2. Gene Variants for Endurance Athlete Status

An individual’s endurance capacity is determined by many factors, including their
muscle fibre typology, haemoglobin mass, mitochondrial biogenesis, maximal cardiac out-
put, and maximal rate of oxygen consumption (VO2max ), among others [118–124]. Indeed,
there is evidence that these intermediate phenotypes have a substantial genetic influence,
with literature indicating that genetic factors account for up to 70% of the variability in
endurance-related traits [125]. Usually, genetic markers associated with endurance athlete
status are determined by comparing allelic frequencies between endurance athletes (e.g.,
biathletes, road cyclists etc.) and controls.
To support the observed findings from endurance-related case-control studies, re-
searchers subsequently perform functional, lab-based studies to determine the relationship
between genotypes and physiological measures. Examples of measurements used to
complement genomic studies include (but are not limited to) VO2max , forced expiratory
volume in one second (FEV1), proportion of slow-twitch muscle fibres, recovery speed,
long-distance running performance, running economy, lactate threshold, erythropoietin
and haemoglobin levels, number of erythrocytes, capillary density, mitochondrial density,
fat metabolism, and fatigue resistance.
Our literature search revealed that at least 41 of the 114 reported markers could be asso-
ciated with endurance athlete status based on our criteria (Table 1). The most promising ge-
netic markers for endurance athlete status include AMPD1 rs17602729 C, CDKN1A rs236448
A, HFE rs1799945 G, MYBPC3 rs1052373 G, NFIA-AS2 rs1572312 C, PPARA rs4253778 G,
and PPARGC1A rs8192678 G alleles. In contrast, the other 73 markers (endurance alle-
les) have not passed our strict criteria: ACOXL rs13027870 G, ADRA2A 6.7kb, ADRA2A
rs1800544 G, ADRB1 rs1801252 G, AGT rs699 A, BDKRB2 rs1799722 T, CAMK1D rs11257754
A, CHRNB3 rs4950 G, CLSTN2 rs2194938 A, CNDP2 rs6566810 A, COL5A1 rs71746744
AGGG, COL6A1 rs35796750 T, CPQ rs6468527 A, CYP2D6 rs3892097 G, DMT1 258 bp,
EPAS1 (HIF2A) rs1867785 G, EPAS1 (HIF2A) rs11689011 T, GABPB1 rs8031031 T, GALM
rs3821023 A, GNB3 rs5443 T, GRM3 rs724225 G, GSTT rs17856199 (+), IGF1R rs1464430
A, IL6 rs1800795 C, IL15RA rs2228059 A, ITPR1 rs1038639 T, ITPR1 rs2131458 T, FMNL2
rs12693407 G, KCNJ11 rs5219 C, L3MBTL4 rs17483463 T, MSTN rs11333758 D, MtDNA
loci (G1, HV, L0, M*, m.11215T, m.152C, m.15518T, m.15874G, m.4343G, m.514(CA) ≤ 4,
poly(C ≥ 7) stretch at m.568–573, m.16080G, m.5178C, N9, V, unfavourable: B, J2, T, L3*),
NALCN-AS1 rs4772341 A, NACC2 rs4409473 C, NATD1 rs732928 G, NOS3 rs1799983 G,
NOS3 (CA)n 164bp, NOS3 27bp 4B, PPARD rs2016520 C, PPARD rs1053049 T, PPARGC1A
rs4697425 A, PPARGC1B rs11959820 A, PPP3CA rs3804358 C, PPP3CB rs3763679 C, SGMS1
rs884880 A, SLC2A4 rs5418 A, SOD2 rs4880 C, SPOCK1 rs1051854 T, TPK1 rs10275875
T, TTN rs10497520 T, Y-chromosome haplogroups (E*, E3*, and K*(xP); unfavourable:
E3b1), and ZNF429 rs1984771 G. Most of these markers have been described in previous
reviews [27,126,127] but cannot be included in our current list of endurance-associated
markers until they are validated through replication by additional studies.
Genes 2023, 14, 1235 6 of 32

Table 1. Genetic markers for endurance athlete status.

References
Polymorphism Endurance-Related Studies with Positive Studies with Negative or
Gene Full Name Locus
Allele Results Controversial Results
Alu I/D (rs4343 A/G
ACE Angiotensin I converting enzyme 17q23.3 I (A or C) [14–16,128–141] [133,142–153]
or rs4341 C/G)
ACTN3 Actinin α 3 11q13.1 rs1815739 C/T T [17,154–156] [152,157–170]
ADRB2 Adrenoceptor β 2 5q31-q32 rs1042713 G/A A [160,171,172] [173,174]
ADRB2 Adrenoceptor β 2 5q31-q32 rs1042714 G/C C [153,175] [173,174]
ADRB3 Adrenoceptor β 3 8p11.23 rs4994 A/G G [170,173]
AGTR2 Angiotensin II receptor type 2 Xq22-q23 rs11091046 A/C C [176] [177]
AQP1 Aquaporin 1 7p14 rs1049305 C/G C [178–180]
Adenosine monophosphate
AMPD1 1p13 rs17602729 C/T C [19,153,181–183] [184]
deaminase 1
BDKRB2 Bradykinin receptor B2 14q32.1-q32.2 +9/−9 (exon 1) –9 [185,186] [153,187–189]
Cyclin Dependent Kinase Inhibitor
CDKN1A 6p21.2 rs236448 A/C A [43]
1A
CKM Creatine kinase M-type 19q13.32 rs8111989 A/G A [190–192] [133,193]
COL5A1 Collagen type V α 1 chain 9q34.2-q34.3 rs12722 C/T T [194,195]
FTO α-Ketoglutarate Dependent
FTO 16q12.2 rs9939609 T/A T [196,197] [198]
Dioxygenase

GA binding protein transcription rs12594956 A/C A [199,200]

GABPB1 15q21.2
factor subunit β 1 rs7181866 A/G G [199,201] [200]
Polypeptide
GALNTL6 4q34.1 rs558129 T/C C [40]
N-acetylgalactosaminyltransferase 6
GSTP1 Glutathione S-transferase Pi 1 11q13.2 rs1695 A/G G [202,203]
HFE Homeostatic iron regulator 6p21.3 rs1799945 C/G G [153,204–207]
Hypoxia inducible factor 1
HIF1A 14q23.2 rs11549465 C/T C [208,209] [144,210]
subunit α
Genes 2023, 14, 1235 7 of 32

Table 1. Cont.

References
Polymorphism Endurance-Related Studies with Positive Studies with Negative or
Gene Full Name Locus
Allele Results Controversial Results
MCT1 Monocarboxylate transporter 1 1p12 rs1049434 A/T T [60,211–214] [215]
H [161,216]
MtDNA loci Mitochondrial DNA MtDNA MtDNA haplogroups
Unfavourable: K [161,216]
MYBPC3 Myosin Binding Protein C3 11p11.2 rs1052373 A/G G [42]
NFATC4 Nuclear factor of activated T cells 4 14q11.2 rs2229309 G/C G [144]
NFIA-AS2 NFIA antisense RNA 2 1p31.3 rs1572312 C/A C [39,46]
NOS3 Nitric oxide synthase 3 7q36 rs2070744 T/C T [153,217,218] [219]
Peroxisome proliferator activated
PPARA 22q13.31 rs4253778 G/C G [20,220–222]
receptor α
Peroxisome proliferative activated
PPARGC1A 4p15.1 rs8192678 G/A G [18,20,170,223] [216,224,225]
receptor, γ, coactivator 1 α
Peroxisome proliferative activated
PPARGC1B 5q32 rs7732671 G/C C [144,226]
receptor, γ, coactivator 1 β
Protein phosphatase 3 regulatory
PPP3R1 2p15 Promoter 5I/5D 5I [144,227]
subunit B, α
PRDM1 PR/SET Domain 1 6q21 rs10499043 C/T T [228,229]
RBFOX1 RNA binding fox-1 homolog 1 16p13.3 rs7191721 G/A G [39]
SIRT1 Sirtuin 1 10q21.3 rs41299232 C/G G [45]
Striated Muscle Enriched Protein
SPEG 2q35 rs7564856 G/A G [230]
Kinase
Transcription factor A,
TFAM 10q21 rs1937 G/C C [144,231] [216]
mitochondrial
Transient Receptor Potential Cation
TRPM2 21q22.3 rs1785440 A/G G [45]
Channel Subfamily M Member 2
Genes 2023, 14, 1235 8 of 32

Table 1. Cont.

References
Polymorphism Endurance-Related Studies with Positive Studies with Negative or
Gene Full Name Locus
Allele Results Controversial Results
Thyroid stimulating hormone
TSHR 14q31 rs7144481 T/C C [39]
receptor
UCP2 Uncoupling protein 2 11q13 rs660339 C/T T [130,144,232]
UCP3 Uncoupling Protein 3 11q13 rs1800849 C/T T [130,144] [233]
Vascular endothelial growth
VEGFA 6p12 rs2010963 G/C C [144,234,235]
factor A
Vascular endothelial growth factor
VEGFR2 4q11-q12 rs1870377 T/A A [236,237]
receptor 2
Genes 2023, 14, 1235 9 of 32

3. Gene Variants for Power Athlete Status

Several characteristics are positively associated with power performance, including
circulating levels of testosterone, percentage and cross-sectional area of fast-twitch muscle
fibres, muscle mass and strength, body and calcaneus height, muscle fascicle length, and
reaction time, among others [3,238–244]. The heritability of power-related phenotypes
has been reported in the literature to range from approximately 49 to 86% in a range of
phenotypes, including jumping ability [245,246]. Typically, genetic markers associated
with power athlete status are determined by comparing allelic frequencies between power
athletes (e.g., 100 m runners, shot putters, arm wrestlers, etc.) and untrained subjects. To
support findings from case-control studies, investigators perform genotype–phenotype
studies by measuring sprint times, jump performance, muscle fibre size, muscle fibre
typology, maximal strength, rate of force development, and circulatory levels of anabolic
hormones such as testosterone. Our literature search revealed that at least 45 of the
95 markers reportedly associated with power athlete status met our new criteria (Table 2).
The most promising of these genetic markers associated with power athlete status currently
include ACTN3 rs1815739 C, AMPD1 rs17602729 C, CDKN1A rs236448 C, CPNE5 rs3213537
G, GALNTL6 rs558129 T, IGF2 rs680 G, IGSF3 rs699785 A, NOS3 rs2070744 T, and TRHR
rs7832552 T alleles. In contrast, the remaining 50 genetic markers (power alleles) did not
meet our strict criteria: ARHGEF28 rs17664695 G, CACNG1 rs1799938 A, CALCR rs17734766
G, CLSTN2 rs2194938 C, CNDP1 rs2887 A, CNDP1 rs2346061 C, CNDP2 rs3764509 G, COTL1
rs7458 T, CREM rs1531550 A, DMD rs939787 T, EPAS1 (HIF2A) rs1867785 G, EPAS1 (HIF2A)
rs11689011 C, FOCAD rs17759424 C, GABRR1 rs282114 A, GALNT13 rs10196189 G, GPC5
rs852918 T, IGF1R rs1464430 C, IL1RN rs2234663 *2, IP6K3 rs6942022 C, MCT1 rs1049434
A, MED4 rs7337521 T, MPRIP rs6502557 A, MtDNA loci (favourable: F, m.204C, m.151T,
m.15314A, Non-L/U6, unfavourable: m.16278T, m.5601T, m.4833G, m.5108C, m.7600A,
m.9377G, m.13563G, m.14200C, m.14569A), MTR rs1805087 G, MTRR rs1801394 G, NOS3
rs1799983 G, NRG1 rs17721043 A, PPARGC1A rs8192678 A, PPARGC1B rs10060424 C,
RC3H1 rs767053 G, SLC6A2 rs1805065 C, SUCLA2 rs10397 A, TPK1 rs10275875 C, UCP2
rs660339 C, VEGFR2 rs1870377 T, WAPL rs4934207 C, and ZNF423 rs11865138 C. The
majority of these markers are reported in previous reviews [25,126,127] and should be
validated in additional studies before they can meet the criteria to be included in our list of
power-associated genetic variants.
Genes 2023, 14, 1235 10 of 32

Table 2. Genetic markers for power athlete status.

References
Polymorphism Power-Related Studies with Negative or
Gene Full Name Locus Studies with Positive Results
Allele Controversial Results
Alu I/D (rs4343 A/G
ACE Angiotensin I converting enzyme 17q23.3 D (G) [16,128,145,169,247–250] [150,251–254]
or rs4341 C/G)
ACVR1B Activin A type IB receptor 12q13.13 rs2854464 A/G A [255,256] [256,257]
ACTN3 Actinin α 3 11q13.1 rs1815739 C/T C [17,161,162,168,170,250,258–264] [159,165,254,265,266]
ADAM Metallopeptidase
ADAM15 1q21.3 rs11264302 G/A G [49]
Domain 15
rs1042713 G/A G [41,174]
ADRB2 Adrenoceptor β 2 5q31-q32
rs1042714 C/G G [41,174]
AGRN Agrin 1p36.33 rs4074992 C/T C [45]
AGT Angiotensinogen 1q42.2 rs699 T/C C [41,267,268]
AGTR2 Angiotensin II receptor type 2 Xq22-q23 rs11091046 A/C A [176,177] [55]
AKAP6 A-Kinase Anchoring Protein 6 14q12 rs12883788 C/T C [49]
Adenosine monophosphate
AMPD1 1p13 rs17602729 C/T C [184,269,270]
deaminase 1
Activator of Transcription and
AUTS2 7q11.22 rs10452738 A/G A [49]
Developmental Regulator AUTS2
BDNF Brain derived neurotrophic factor 11p14.1 rs10501089 G/A A [271]
Chaperonin Containing TCP1
CCT3 1q22 rs11548200 T/C T [49]
Subunit 3
Cyclin Dependent Kinase
CDKN1A 6p21.2 rs236448 A/C C [43]
Inhibitor 1A
CKM Creatine kinase, M-type 19q13.32 rs8111989 A/G G [65,272,273] [274]
CNTFR Ciliary neurotrophic factor receptor 9p13.3 rs41274853 C/T T [275]
Genes 2023, 14, 1235 11 of 32

Table 2. Cont.

References
Polymorphism Power-Related Studies with Negative or
Gene Full Name Locus Studies with Positive Results
Allele Controversial Results
CPNE5 Copine V 6p21.2 rs3213537 G/A G [41,48]
CRTAC1 Cartilage Acidic Protein 1 10q24.2 rs2439823 A/G A [49]
CREB Regulated Transcription
CRTC1 19p13.11 rs11881338 T/A A [49]
Coactivator 1
E2F3 E2F Transcription Factor 3 6p22.3 rs4134943 C/T T [49]
FHL2 Four and a Half LIM Domains 2 2q12.2 rs55680124 C/T C [49]
Polypeptide
GALNTL6 N-acetylgalactosaminyltransferase 4q34.1 rs558129 C/T T [47,276]
like 6
GDF5 Growth Differentiation Factor 5 20q11.22 rs143384 A/G G [49]
Hypoxia inducible factor 1 α
HIF1A 14q21-q24 rs11549465 C/T T [277–279]
subunit
Hydroxysteroid 17-β
HSD17B14 19q13.33 rs7247312 A/G G [41]
dehydrogenase 14
IGF1 Insulin like growth factor 1 12q23.2 rs35767 C/T T [280,281]
IGF2 Insulin like growth factor 2 11p15.5 rs680 A/G G [41,281,282]
Immunoglobulin Superfamily
IGSF3 1p13.1 rs699785 G/A A [49]
Member 3
IL6 Interleukin 6 7p21 rs1800795 C/G G [41,283,284]
Inflammation and Lipid Regulator
ILRUN with UBA-Like and NBR1-Like 6p21.31 rs205262 A/G A [49]
Domains
Methylenetetrahydrofolate
MTHFR 1p36.3 rs1801131 A/C C [285,286]
reductase
NOS3 Nitric oxide synthase 3 7q36 rs2070744 T/C T [219,279,287]
Genes 2023, 14, 1235 12 of 32

Table 2. Cont.

References
Polymorphism Power-Related Studies with Negative or
Gene Full Name Locus Studies with Positive Results
Allele Controversial Results
NRXN3 Neurexin 3 14q24.3-q31.1 rs8011870 G/A G [49]
NUP210 Nucleoporin 210 3p25.1 rs2280084 C/A C [45]
Piezo Type Mechanosensitive Ion rs572934641 (TCC/-)
PIEZO1 16q24.3 D [288]
Channel Component 1 E756del
Peroxisome proliferator activated
PPARA 22q13.31 rs4253778 G/C C [159,220,289]
receptor α

Peroxisome proliferator activated rs1801282 C/G G [279,290,291] [292]

PPARG 3p25.2
receptor γ rs2920503 C/T T [49]
SLC39A8 Solute Carrier Family 39 Member 8 4q24 rs13107325 C/T C [49]
SOD2 Superoxide dismutase 2 6q25.3 rs4880 C/T C [293]
Thyrotropin releasing hormone
TRHR 8q23.1 rs7832552 C/T T [65,294,295]
receptor

Ubiquitin Protein Ligase E3 rs10505025 G/A A [296]

UBR5 8q22.3
Component N-Recognin 5 rs4734621 G/A A [296]
ZNF568 Zinc Finger Protein 568 19q13.12 rs1667369 A/C A [49]
Genes 2023, 14, 1235 13 of 32

4. Gene Variants for Strength Athlete Status

Performance in strength-based sports is based on multiple factors. However, the fac-
tors considered to contribute substantially to strength phenotypes include skeletal muscle
hypertrophy (muscle fibre size), hyperplasia, the predominance of fast-twitch muscle fibres,
a greater muscle fascicle pennation angle, improved neurological adaptation, high gly-
colytic capacity, and increased circulatory testosterone [297]. Importantly, evidence exists
that strength athletes exhibit vastly different transcriptomic, biochemical, anthropometric,
physiological, and biomechanical characteristics compared to endurance athletes and/or
controls [1,4]. These differences can be explained by the presence of both deliberate envi-
ronmental (training, nutrition, etc.) and genetic factors. Indeed, studies indicate that there
is a strong heritability of power- and strength-related traits, where genetic factors account
for up to 85% of the variation in maximal isometric, isotonic, and isokinetic strength [246].
In a recent study investigating the genetic component of severe sarcopenia (the age-related
decline in skeletal muscle mass, strength, and gait speed) [37], it was found that the alleles
associated with higher risk of severe sarcopenia were closely linked to tiredness, alcohol
intake, smoking, time spent watching television, and a higher self-reported consumption of
salt and processed meat. In contrast, alleles associated with lower risk of severe sarcopenia
were positively associated with levels of serum testosterone, IGF1, and 25-hydroxyvitamin
D; height; physical activity; as well as indicators of healthier dietary habits (self-reported in-
take of cereal, cheese, oily fish, protein, water, fruit, and vegetables). Whilst muscle strength
phenotypes in the general population may be less pronounced than in strength athletes,
the latter may represent an ideal population to identify genomic variants associated with
skeletal muscle capacity, potentially aiding the advancement of knowledge surrounding
sarcopenia and directing strategies to reduce the negative impact of age-related declines
in muscle mass. In general, genetic markers associated with strength athlete status can be
determined by comparing allelic frequencies between strength athletes and controls. To
support these findings, scientists perform genotype–phenotype studies by measuring hand-
grip and isokinetic strength, powerlifting/weightlifting performance, as well as evaluating
the acute and chronic responses to resistance training.
Previously, 170 DNA polymorphisms were reported to be associated with handgrip
strength in three large GWASs [34–36]. In a follow-up study involving elite weightlifters
and powerlifters, Moreland et al. [51] tested the hypothesis that alleles associated with
greater handgrip strength would be over-represented in these athletes compared to controls.
Accordingly, they identified 23 DNA polymorphisms that were associated with strength
athlete status. Of these SNPs, the LRPPRC rs10186876, MMS22L rs9320823, and PHACTR1
rs6905419 polymorphisms were also associated with superior competitive weightlifting
performance [298].
Our literature search based on our new inclusion criteria revealed at that least 42 ge-
netic markers could be associated with strength athlete status (Table 3). The most promising
genetic markers for strength athlete status include ACTN3 rs1815739 C, AR ≥ 21 CAG
repeats, LRPPRC rs10186876 A, MMS22L rs9320823 T, PHACTR1 rs6905419 C, and PPARG
rs1801282 G alleles.
Genes 2023, 14, 1235 14 of 32

Table 3. Genetic markers for strength athlete status.

References
Polymorphism Strength-Related Studies with Positive Studies with Negative or
Gene Full Name Locus
Allele Results Controversial Results
ABHD17C Abhydrolase domain containing 17C 15q25.1 rs7165759 G/A A [35,51]
Alu I/D (rs4343 A/G
ACE Angiotensin I converting enzyme 17q23.3 D (G) [299–304] [305]
or rs4341 C/G)
ACTG1 Actin γ 1 17q25.3 rs6565586 T/A A [34,51]
ACTN3 Actinin α 3 11q13.1 rs1815739 C/T C [302,306–308] [51,305,309,310]
ADCY3 Adenylate cyclase 3 2p23.3 rs10203386 T/A T [35,51]
ADPGK ADP dependent glucokinase 15q24.1 rs4776614 C/G C [35,51]
AGT Angiotensinogen 1q42.2 rs699 T/C C [310,311] [51]
Aldehyde Dehydrogenase 2 Family
ALDH2 12q24.12 rs671 G/A G [66–68]
Member
ANGPT2 Angiopoietin 2 8p23.1 rs890022 G/A A [51,312]
AR Androgen Receptor Xq12 (CAG)n ≥21 [313,314]
ARPP21 CAMP regulated phosphoprotein 21 3p22.3 rs1513475 T/C C [35,51]
Bicoid interacting 3 domain containing
BCDIN3D 12q13.12 rs12367809 C/T C [35,51]
RNA methyltransferase
CKM Creatine kinase, M-type 19q13.32 rs8111989 A/G G [54,315] [51,274]
CNTFR Ciliary neurotrophic factor receptor 9p13.3 rs41274853 C/T T [275,316] [51]
CRTAC1 Cartilage acidic protein 1 10q24.2 rs563296 G/A G [35,51]
Dihydroorotate dehydrogenase
DHODH 16q22.2 rs12599952 G/A A [35,51]
(Quinone)
Polypeptide
GALNTL6 4q34.1 rs558129 C/T T [47]
N-acetylgalactosaminyltransferase-like 6
GBE1 1, 4-α-glucan branching enzyme 1 3p12.2 rs9877408 A/G A [35,51]
Golgi brefeldin A resistant guanine
GBF1 10q24.32 rs2273555 G/A A [34,317]
nucleotide exchange factor 1
Genes 2023, 14, 1235 15 of 32

Table 3. Cont.

References
Polymorphism Strength-Related Studies with Positive Studies with Negative or
Gene Full Name Locus
Allele Results Controversial Results
GLIS3 GLIS Family Zinc Finger 3 9p24.2 rs34706136 T/TG TG [50]
HIF1A Hypoxia inducible factor 1 α 14q21-q24 rs11549465 C/T T [278,295,318] [51]
IGF1 Insulin-like growth factor 1 12q23.2 rs35767 C/T T [51,280,319]
IL6 Interleukin 6 7p21 rs1800795 C/G G [51,283]
Inositol 1, 4, 5-Triphosphate Receptor
ITPR1 3p26.1 rs901850 G/T T [35,51]
Type 1
KIF1B Kinesin family member 1B 1p36.22 rs11121542 G/A G [35,51]
Leucine-rich pentatricopeptide repeat
LRPPRC 2p21 rs10186876 A/G A [34,51,298]
cassette
MLN Motilin 6p21.31 rs12055409 A/G G [35,317]
Methyl methanesulfonate-sensitivity
MMS22L 6q16.1 rs9320823 T/C T [35,51,298]
protein 22-Like
MTHFR Methylenetetrahydrofolate reductase 1p36.3 rs1801131 A/C C [51,286,298]
Nuclear pore complex interacting protein
NPIPB6 16p12.1 rs2726036 A/C A [35,51]
family member B6
PHACTR1 Phosphate and actin regulator 1 6p24.1 rs6905419 C/T C [35,51,298]
Pleckstrin homology domain containing
PLEKHB1 11q13.4 rs7128512 A/G G [51,312]
B1
Peroxisome proliferator activated
PPARA 22q13.31 rs4253778 G/C C [220,320,321] [51]
receptor α
Peroxisome proliferator activated
PPARG 3p25.2 rs1801282 C/G G [51,290,291]
receptor γ
Peroxisome proliferative activated
PPARGC1A 4p15.2 rs8192678 G/A A [51,305,308]
receptor, γ, coactivator 1 α
R3HDM1 R3H domain containing 1 2q21.3 rs6759321 G/T T [35,51]
Ras protein specific guanine nucleotide
RASGRF1 15q25.1 rs1521624 C/A A [35,51]
Releasing Factor 1
Genes 2023, 14, 1235 16 of 32

Table 3. Cont.

References
Polymorphism Strength-Related Studies with Positive Studies with Negative or
Gene Full Name Locus
Allele Results Controversial Results
RMC1 Regulator of MON1-CCZ1 18q11.2 rs303760 C/T C [35,51]
SLC39A8 Solute carrier family 39 member 8 4q24 rs13135092 A/G A [35,51]
TFAP2D Transcriptional factor AP-2 delta 6p12.3 rs56068671 G/T T [35,51]
Zinc finger with KRAB and SCAN
ZKSCAN5 7q22.1 rs3843540 T/C C [35,51]
domains 5
ZNF608 Zinc finger protein 608 5q23.2 rs4626333 G/A G [312,317]
 Genes 2023, 14, 1235 17 of 32

5. Conclusions
The current review demonstrates that at least 251 genetic markers are reportedly linked
to sport-related traits. However, only 128 (51%) of these markers (41 endurance-related,
45 power-related, and 42 strength-related) have been associated with athlete status in two
Difficult to test due to or more studies. On the other hand, of these 128 genetic markers, the significance of 29
variability researchers (22.7%) DNA polymorphisms was not replicated in at least one study, raising the possibility
and participants, that a number of findings may represent false positives. It is important to consider that
adherence, there may be one of several reasons why the findings of a study may not be replicated
complicated definition, by another, including disparity of sample sizes, small sample sizes in one or more of the
studies, different study designs, inconsistent classification of sporting groups or types
etc
of sport (strength, power, etc.), variability in how researchers or research groups define
the term “elite athletes” (some researchers define the term “elite” as performances at the
international level, others if the athlete is a prize winner in international competitions), and
the ethnicity/geographical ancestry of the cohorts studied, amongst others.
As discussed previously, height remains not only the most studied exercise-related
phenotype at the genetic level, but also the most studied human trait, with 12,111 associated
SNPs [31]. It is estimated that the final number of height-related SNPs may reach 25,000
(with a minor allele frequency of ≥1%), but the sample size needs to be increased to
approximately 100 million individuals of the same ethnicity. These values should be
noteworthy and serve as a benchmark for the direction of future research in the field of
sports genomics, where the current number of 251 genetic markers must be increased by
a considerable magnitude in order to fully comprehend the genomic underpinnings of
exercise performance, and thus to be considered as potential predictors of talent in sport.
Given that effective talent identification remains a challenging task despite decades of
research and strategy [322–324], it remains possible that the development of predictive
genetic performance tests in future may be able to contribute to the advancement of this
field. However, the literature currently available does not support the use of genetic testing
for these purposes [325–327].
Whilst genomics is the among the most established molecular sub-disciplines of sport
and exercise research, sport- and exercise-related DNA polymorphisms do not fully ex-
plain the heritability of athlete status. Consequently, other forms of variation, such as rare
mutations [328,329] and epigenetic markers (i.e., stable and heritable changes in gene ex-
pression) [330], must be considered. Newly emerging high-throughput technologies enable
the design of multi-omics approaches integrating various -omics levels (metabolomics,
transcriptomics, proteomics, epigenomics, etc.) with the aim of determining how each
level contributes to the biological mechanisms underpinning physical performance. For
example, transcriptomic analyses have revealed the roles of both genomic and epigenomic
mechanisms in modulating the transcription of genes regulated by exercise [2,331,332].
Incorporating multi-omics approaches has the potential to drastically advance the under-
standing of how the acute response to exercise is regulated, and consequently how chronic
adaptations to exercise are mediated in the context of elite performance and/or health and
wellbeing. Accordingly, future research, including collaborative multicentre GWASs and
whole-genome sequencing of large athlete cohorts with further validation and replication,
as well as the use of large purpose-built Biobanks, should focus on identifying genetic and
other -omics markers of sport-related phenotypes and their underlying biology.
Our review does have limitations. First, we have not provided information regarding
genetic markers associated with team (game) and combat sports, flexibility, coordination,
personality, cognitive abilities, muscle fibre composition, skeletal muscle hypertrophy,
injuries, and responses to training/supplements. These markers are well described else-
where [4,24,26,28,37,61,74,79,115–117,333,334]. Second, we have not described all studies
in detail (ethnicity, specific sporting disciplines, sample size, p-values etc.) given word
limit. Third, some genetic markers (out of the 128 most significant) were selected based on
data obtained in case-control studies only, without confirmation of functional significance
(genotype–phenotype studies are therefore warranted).
Genes 2023, 14, 1235 18 of 32

In conclusion, our literature search revealed at least 251 DNA polymorphisms that
could be associated with endurance, power, and strength athlete statuses. Most of these
genetic markers have been discovered in studies involving Australian, Brazilian, British,
Canadian, Chinese, Croatian, Czech, Ethiopian, Finnish, French, German, Greek, Hungar-
ian, Indian, Iranian, Israeli, Italian, Jamaican, Japanese, Kenyan, Korean, Lithuanian, Polish,
Qatari, Russian, Slovenian, South African, Spanish, Taiwanese, Tatar, Tunisian, Turkish,
Ukrainian, and US athletes.

Author Contributions: Conceptualization, I.I.A.; formal analysis, E.A.S. and I.I.A.; writing—original
draft preparation, E.A.S. and I.I.A.; writing—review and editing, E.C.R.H. All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Stepto, N.K.; Coffey, V.G.; Carey, A.L.; Ponnampalam, A.P.; Canny, B.J.; Powell, D.; Hawley, J.A. Global Gene Expression in
Skeletal Muscle from Well-Trained Strength and Endurance Athletes. Med. Sci. Sport. Exerc. 2009, 41, 546–565. [CrossRef]
[PubMed]
2. Zhelankin, A.V.; Iulmetova, L.N.; Ahmetov, I.I.; Generozov, E.V.; Sharova, E.I. Diversity and Differential Expression of MicroRNAs
in the Human Skeletal Muscle with Distinct Fiber Type Composition. Life 2023, 13, 659. [CrossRef] [PubMed]
3. Ahmetov, I.I.; Stepanova, A.A.; Biktagirova, E.M.; Semenova, E.A.; Shchuplova, I.S.; Bets, L.V.; Andryushchenko, L.B.; Borisov,
O.V.; Andryushchenko, O.N.; Generozov, E.V.; et al. Is testosterone responsible for athletic success in female athletes? J. Sport.
Med. Phys. Fit. 2020, 60, 1377–1382. [CrossRef]
4. Fuku, N.; Kumagai, H.; Ahmetov, I.I. Genetics of muscle fiber composition. In Sports, Exercise, and Nutritional Genomics: Current
Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 295–314. [CrossRef]
5. Hall, E.C.R.; Semenova, E.A.; Borisov, O.V.; Andryushchenko, O.N.; Andryushchenko, L.B.; Zmijewski, P.; Generozov, E.V.;
Ahmetov, I.I. Association of muscle fiber composition with health and exercise-related traits in athletes and untrained subjects.
Biol. Sport 2021, 38, 659–666. [CrossRef] [PubMed]
6. Rees, T.; Hardy, L.; Güllich, A.; Abernethy, B.; Côté, J.; Woodman, T.; Montgomery, H.; Laing, S.; Warr, C. The Great British
Medalists Project: A Review of Current Knowledge on the Development of the World’s Best Sporting Talent. Sport. Med. 2016, 46,
1041–1058. [CrossRef]
7. Blume, K.; Wolfarth, B. Identification of Potential Performance-Related Predictors in Young Competitive Athletes. Front. Physiol.
2019, 10, 1394. [CrossRef]
8. Dines, H.R.; Nixon, J.; Lockey, S.J.; Herbert, A.J.; Kipps, C.; Pedlar, C.R.; Day, S.H.; Heffernan, S.M.; Antrobus, M.R.; Brazier,
J.; et al. Collagen Gene Polymorphisms Previously Associated with Resistance to Soft-Tissue Injury Are More Common in
Competitive Runners Than Nonathletes. J. Strength Cond. Res. 2023, 37, 799–805. [CrossRef]
9. De Moor, M.H.M.; Spector, T.D.; Cherkas, L.F.; Falchi, M.; Hottenga, J.J.; Boomsma, D.I.; de Geus, E.J.C. Genome-wide linkage
scan for athlete status in 700 British female DZ twin pairs. Twin Res. Hum. Genet. 2007, 10, 812–820. [CrossRef]
10. Macnamara, B.N.; Hambrick, D.Z.; Oswald, F.L. Deliberate practice and performance in music, games, sports, education, and
professions: A meta-analysis. Psychol. Sci. 2014, 25, 1608–1618. [CrossRef]
11. Beck, K.L.; Thomson, J.S.; Swift, R.J.; von Hurst, P.R. Role of nutrition in performance enhancement and postexercise recovery.
Open Access J. Sports Med. 2015, 6, 259–267. [CrossRef]
12. Bezuglov, E.; Morgans, R.; Butovskiy, M.; Emanov, A.; Shagiakhmetova, L.; Pirmakhanov, B.; Waśkiewicz, Z.; Lazarev, A. The
relative age effect is widespread among European adult professional soccer players but does not affect their market value. PLoS
ONE 2023, 18, e0283390. [CrossRef]
13. Rivera, M.A.; Dionne, F.T.; Wolfarth, B.; Chagnon, M.; Simoneau, J.A.; Pérusse, L.; Boulay, M.R.; Gagnon, J.; Song, T.M.; Keul,
J.; et al. Muscle-specific creatine kinase gene polymorphisms in elite endurance athletes and sedentary controls. Med. Sci. Sport.
Exerc. 1997, 29, 1444–1447. [CrossRef]
14. Montgomery, H.E.; Marshall, R.; Hemingway, H.; Myerson, S.; Clarkson, P.; Dollery, C.; Hayward, M.; Holliman, D.E.; World, M.;
Thomas, E.L.; et al. Human gene for physical performance. Nature 1998, 393, 221–222. [CrossRef]
15. Gayagay, G.; Yu, B.; Hambly, B.; Boston, T.; Hahn, A.; Celermajer, D.S.; Trent, R.J. Elite endurance athletes and the ACE I allele--the
role of genes in athletic performance. Hum. Genet. 1998, 103, 48–50. [CrossRef]
Genes 2023, 14, 1235 19 of 32

16. Nazarov, I.B.; Woods, D.R.; Montgomery, H.E.; Shneider, O.V.; Kazakov, V.I.; Tomilin, N.V.; Rogozkin, V.A. The angiotensin
converting enzyme I/D polymorphism in Russian athletes. Eur. J. Hum. Genet. 2001, 9, 797–801. [CrossRef]
17. Yang, N.; MacArthur, D.G.; Gulbin, J.P.; Hahn, A.G.; Beggs, A.H.; Easteal, S.; North, K. ACTN3 genotype is associated with
human elite athletic performance. Am. J. Hum. Genet. 2003, 73, 627–631. [CrossRef]
18. Lucia, A.; Gómez-Gallego, F.; Barroso, I.; Rabadán, M.; Bandrés, F.; San Juan, A.F.; Chicharro, J.L.; Ekelund, U.; Brage, S.; Earnest,
C.P.; et al. PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men. J. Appl. Physiol. 2005, 99,
344–348. [CrossRef]
19. Rubio, J.C.; Martín, M.A.; Rabadán, M.; Gómez-Gallego, F.; San Juan, A.F.; Alonso, J.M.; Chicharro, J.L.; Pérez, M.; Arenas, J.;
Lucia, A. Frequency of the C34T mutation of the AMPD1 gene in world-class endurance athletes: Does this mutation impair
performance? J. Appl. Physiol. 2005, 98, 2108–2112. [CrossRef]
20. Akhmetov, I.I.; Popov, D.V.; Mozhaı̆skaia, I.A.; Missina, S.S.; Astratenkova, I.V.; Vinogradova, O.L.; Rogozkin, V.A. Association of
regulatory genes polymorphisms with aerobic and anaerobic performance of athletes. Ross. Fiziol. Zh. Im. I.M. Sechenova 2007, 93,
837–843.
21. Akhmetov, I.I.; Astranenkova, I.V.; Rogozkin, V.A. Association of PPARD gene polymorphism with human physical performance.
Mol. Biol. 2007, 41, 852–857.
22. Bray, M.S.; Hagberg, J.M.; Pérusse, L.; Rankinen, T.; Roth, S.M.; Wolfarth, B.; Bouchard, C. The human gene map for performance
and health-related fitness phenotypes: The 2006–2007 update. Med. Sci. Sports Exerc. 2009, 41, 35–73. [CrossRef] [PubMed]
23. Gineviciene, V.; Utkus, A.; Pranckevičienė, E.; Semenova, E.A.; Hall, E.C.R.; Ahmetov, I.I. Perspectives in Sports Genomics.
Biomedicines 2022, 10, 298. [CrossRef] [PubMed]
24. Cagnin, S.; Chemello, F.; Ahmetov, I.I. Genes and response to aerobic training. In Sports, Exercise, and Nutritional Genomics: Current
Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 169–188. [CrossRef]
25. Maciejewska-Skrendo, A.; Sawczuk, M.; Ci˛eszczyk, P.; Ahmetov, I.I. Genes and power athlete status. In Sports, Exercise, and
Nutritional Genomics: Current Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA,
2019; pp. 41–72. [CrossRef]
26. Massidda, M.; Calò, C.M.; Ci˛eszczyk, P.; Kikuchi, N.; Ahmetov, I.I.; Williams, A.G. Genetics of Team Sports. In Sports, Exercise, and
Nutritional Genomics: Current Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA,
2019; pp. 105–128. [CrossRef]
27. Semenova, E.A.; Fuku, N.; Ahmetov, I.I. Genetic profile of elite endurance athletes. In Sports, Exercise, and Nutritional Genomics:
Current Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 73–104.
[CrossRef]
28. Valeeva, E.V.; Ahmetov, I.I.; Rees, T. Psychogenetics and sport. In Sports, Exercise, and Nutritional Genomics: Current Status and
Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 147–165. [CrossRef]
29. Varillas-Delgado, D.; Del Coso, J.; Gutiérrez-Hellín, J.; Aguilar-Navarro, M.; Muñoz, A.; Maestro, A.; Morencos, E. Genetics and
sports performance: The present and future in the identification of talent for sports based on DNA testing. Eur. J. Appl. Physiol.
2022, 122, 1811–1830. [CrossRef] [PubMed]
30. Wang, G.; Tanaka, M.; Eynon, N.; North, K.N.; Williams, A.G.; Collins, M.; Moran, C.N.; Britton, S.L.; Fuku, N.; Ashley, E.A.; et al.
The Future of Genomic Research in Athletic Performance and Adaptation to Training. Genet. Sport. 2016, 61, 55–67. [CrossRef]
31. Yengo, L.; Vedantam, S.; Marouli, E.; Sidorenko, J.; Bartell, E.; Sakaue, S.; Graff, M.; Eliasen, A.U.; Jiang, Y.; Raghavan, S.; et al. A
saturated map of common genetic variants associated with human height. Nature 2022, 610, 704–712. [CrossRef]
32. Pei, Y.F.; Liu, Y.Z.; Yang, X.L.; Zhang, H.; Feng, G.J.; Wei, X.T.; Zhang, L. The genetic architecture of appendicular lean mass
characterized by association analysis in the UK Biobank study. Commun. Biol. 2020, 3, 608. [CrossRef]
33. Ruth, K.S.; Day, F.R.; Tyrrell, J.; Thompson, D.J.; Wood, A.R.; Mahajan, A.; Beaumont, R.N.; Wittemans, L.; Martin, S.; Busch,
A.S.; et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nat. Med. 2020, 26,
252–258. [CrossRef]
34. Willems, S.M.; Wright, D.J.; Day, F.R.; Trajanoska, K.; Joshi, P.K.; Morris, J.A.; Matteini, A.M.; Garton, F.C.; Grarup, N.; Oskolkov,
N.; et al. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nat.
Commun. 2017, 8, 16015. [CrossRef]
35. Tikkanen, E.; Gustafsson, S.; Amar, D.; Shcherbina, A.; Waggott, D.; Ashley, E.A.; Ingelsson, E. Biological Insights into Mus-cular
Strength: Genetic Findings in the UK Biobank. Sci. Rep. 2018, 8, 6451. [CrossRef]
36. Jones, G.; Trajanoska, K.; Santanasto, A.J.; Stringa, N.; Kuo, C.L.; Atkins, J.L.; Lewis, J.R.; Duong, T.; Hong, S.; Biggs, M.L.; et al.
Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women. Nat. Commun. 2021,
12, 654. [CrossRef]
37. Semenova, E.A.; Pranckevičienė, E.; Bondareva, E.A.; Gabdrakhmanova, L.J.; Ahmetov, I.I. Identification and Characterization of
Genomic Predictors of Sarcopenia and Sarcopenic Obesity Using UK Biobank Data. Nutrients 2023, 15, 758. [CrossRef]
38. Timmins, I.R.; Zaccardi, F.; Nelson, C.P.; Franks, P.W.; Yates, T.; Dudbridge, F. Genome-wide association study of self-reported
walking pace suggests beneficial effects of brisk walking on health and survival. Commun. Biol. 2020, 3, 634. [CrossRef]
39. Ahmetov, I.; Kulemin, N.; Popov, D.; Naumov, V.; Akimov, E.; Bravy, Y.; Egorova, E.; Galeeva, A.; Generozov, E.; Kostryukova,
E.; et al. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance. Biol.
Sport 2015, 32, 3–9. [CrossRef]
Genes 2023, 14, 1235 20 of 32

40. Rankinen, T.; Fuku, N.; Wolfarth, B.; Wang, G.; Sarzynski, M.A.; Alexeev, D.G.; Ahmetov, I.I.; Boulay, M.R.; Cieszczyk, P.; Eynon,
N.; et al. No evidence of a common DNA variant profile specific to world class endurance athletes. PLoS ONE 2016, 11, e0147330.
[CrossRef]
41. Pickering, C.; Suraci, B.; Semenova, E.A.; Boulygina, E.A.; Kostryukova, E.S.; Kulemin, N.A.; Borisov, O.V.; Khabibova, S.A.; Larin,
A.K.; Pavlenko, A.V.; et al. A genome-wide association study of sprint performance in elite youth football players. J. Strength
Cond. Res. 2019, 33, 2344–2351. [CrossRef]
42. Al-Khelaifi, F.; Yousri, N.A.; Diboun, I.; Semenova, E.A.; Kostryukova, E.S.; Kulemin, N.A.; Borisov, O.V.; Andryushchenko,
L.B.; Larin, A.K.; Generozov, E.V.; et al. Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene
Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism. Front. Genet. 2020, 11, 595. [CrossRef]
43. Semenova, E.A.; Zempo, H.; Miyamoto-Mikami, E.; Kumagai, H.; Larin, A.K.; Sultanov, R.I.; Babalyan, K.A.; Zhelankin, A.V.;
Tobina, T.; Shiose, K.; et al. Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber
Composition. Cells 2022, 11, 3910. [CrossRef]
44. Boulygina, E.A.; Borisov, O.V.; Valeeva, E.V.; Semenova, E.A.; Kostryukova, E.S.; Kulemin, N.A.; Larin, A.K.; Nabiullina, R.M.;
Mavliev, F.A.; Akhatov, A.M.; et al. Whole genome sequencing of elite athletes. Biol. Sport 2020, 37, 295–304. [CrossRef]
45. Bulgay, C.; Kasakolu, A.; Kazan, H.H.; Mijaica, R.; Zorba, E.; Akman, O.; Bayraktar, I.; Ekmekci, R.; Koncagul, S.; Ulucan, K.; et al.
Exome-Wide Association Study of Competitive Performance in Elite Athletes. Genes 2023, 14, 660. [CrossRef]
46. Malczewska-Lenczowska, J.; Orysiak, J.; Majorczyk, E.; Sitkowski, D.; Starczewski, M.; Zmijewski, P. HIF-1α and NFIA-AS2
Polymorphisms as Potential Determinants of Total Hemoglobin Mass in Endurance Athletes. J. Strength Cond. Res. 2022, 36,
1596–1604. [CrossRef]
47. Díaz Ramírez, J.; Álvarez-Herms, J.; Castañeda-Babarro, A.; Larruskain, J.; Ramírez de la Piscina, X.; Borisov, O.V.; Semenova,
E.A.; Kostryukova, E.S.; Kulemin, N.A.; Andryushchenko, O.N.; et al. The GALNTL6 Gene rs558129 Polymorphism is Associated
with Power Performance. J. Strength Cond. Res. 2020, 34, 3031–3036. [CrossRef] [PubMed]
48. Guilherme, J.P.L.F.; Semenova, E.A.; Zempo, H.; Martins, G.L.; Lancha-Junior, A.H.; Miyamoto-Mikami, E.; Kumagai, H.; Tobina,
T.; Shiose, K.; Kakigi, R.; et al. Are Genome-Wide Association Study Identified Single-Nucleotide Polymorphisms Associated with
Sprint Athletic Status? A Replication Study With 3 Different Cohorts. Int. J. Sport. Physiol. Perform. 2021, 16, 489–495. [CrossRef]
[PubMed]
49. Guilherme, J.P.L.F.; Semenova, E.A.; Larin, A.K.; Yusupov, R.A.; Generozov, E.V.; Ahmetov, I.I. Genomic Predictors of Brisk
Walking Are Associated with Elite Sprinter Status. Genes 2022, 13, 1710. [CrossRef] [PubMed]
50. Guilherme, J.P.L.; Semenova, E.A.; Borisov, O.V.; Larin, A.K.; Moreland, E.; Generozov, E.V.; Ahmetov, I.I. Genomic predictors
of testosterone levels are associated with muscle fiber size and strength. Eur. J. Appl. Physiol. 2022, 122, 415–423. [CrossRef]
[PubMed]
51. Moreland, E.; Borisov, O.V.; Semenova, E.A.; Larin, A.K.; Andryushchenko, O.N.; Andryushchenko, L.B.; Generozov, E.V.;
Williams, A.G.; Ahmetov, I.I. Polygenic Profile of Elite Strength Athletes. J. Strength Cond. Res. 2022, 36, 2509–2514. [CrossRef]
52. Ma, F.; Yang, Y.; Li, X.; Zhou, F.; Gao, C.; Li, M.; Gao, L. The association of sport performance with ACE and ACTN3 genetic
polymorphisms: A systematic review and meta-analysis. PLoS ONE 2013, 8, e54685. [CrossRef]
53. Lopez-Leon, S.; Tuvblad, C.; Forero, D.A. Sports genetics: The PPARA gene and athletes’ high ability in endurance sports. A
systematic review and meta-analysis. Biol. Sport 2016, 33, 3–6. [CrossRef]
54. Chen, C.; Sun, Y.; Liang, H.; Yu, D.; Hu, S. A meta-analysis of the association of CKM gene rs8111989 polymorphism with sport
performance. Biol. Sport 2017, 34, 323–330. [CrossRef]
55. Yvert, T.P.; Zempo, H.; Gabdrakhmanova, L.J.; Kikuchi, N.; Miyamoto-Mikami, E.; Murakami, H.; Naito, H.; Cieszczyk, P.;
Leznicka, K.; Kostryukova, E.S.; et al. AGTR2 and sprint/power performance: A case-control replication study for rs11091046
polymorphism in two ethnicities. Biol. Sport 2018, 35, 105–109. [CrossRef]
56. Weyerstraß, J.; Stewart, K.; Wesselius, A.; Zeegers, M. Nine genetic polymorphisms associated with power athlete status—A
Meta-Analysis. J. Sci. Med. Sport 2018, 21, 213–220. [CrossRef]
57. Chen, Y.; Wang, D.; Yan, P.; Yan, S.; Chang, Q.; Cheng, Z. Meta-analyses of the association between the PPARGC1A Gly482Ser
polymorphism and athletic performance. Biol. Sport 2019, 36, 301–309. [CrossRef]
58. Tharabenjasin, P.; Pabalan, N.; Jarjanazi, H. Association of the ACTN3 R577X (rs1815739) polymorphism with elite power sports:
A meta-analysis. PLoS ONE 2019, 14, e0217390. [CrossRef]
59. Tharabenjasin, P.; Pabalan, N.; Jarjanazi, H. Association of PPARGC1A Gly428Ser (rs8192678) polymorphism with potential for
athletic ability and sports performance: A meta-analysis. PLoS ONE 2019, 14, e0200967. [CrossRef]
60. Guilherme, J.P.L.F.; Bosnyák, E.; Semenova, E.A.; Szmodis, M.; Griff, A.; Móra, Á.; Almási, G.; Trájer, E.; Udvardy, A.; Kostryukova,
E.S.; et al. The MCT1 gene Glu490Asp polymorphism (rs1049434) is associated with endurance athlete status, lower blood lactate
accumulation and higher maximum oxygen uptake. Biol. Sport 2021, 38, 465–474. [CrossRef]
61. McAuley, A.B.T.; Hughes, D.C.; Tsaprouni, L.G.; Varley, I.; Suraci, B.; Roos, T.R.; Herbert, A.J.; Kelly, A.L. The association of the
ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: A systematic review and meta-analysis. J. Sport. Sci.
2021, 39, 200–211. [CrossRef]
62. Ipekoglu, G.; Bulbul, A.; Cakir, H.I. A meta-analysis on the association of ACE and PPARA gene variants and endurance athletic
status. J. Sport. Med. Phys. Fitness 2022, 62, 795–802. [CrossRef]
Genes 2023, 14, 1235 21 of 32

63. Konopka, M.J.; van den Bunder, J.C.M.L.; Rietjens, G.; Sperlich, B.; Zeegers, M.P. Genetics of long-distance runners and road
cyclists-A systematic review with meta-analysis. Scand. J. Med. Sci. Sport. 2022, 32, 1414–1429. [CrossRef]
64. Saito, M.; Ginszt, M.; Semenova, E.A.; Massidda, M.; Huminska-Lisowska, K.; Michałowska-Sawczyn, M.; Homma, H.; Ci˛eszczyk,
P.; Okamoto, T.; Larin, A.K.; et al. Is COL1A1 Gene rs1107946 Polymorphism Associated with Sport Climbing Status and
Flexibility? Genes 2022, 13, 403. [CrossRef]
65. Saito, M.; Ginszt, M.; Semenova, E.A.; Massidda, M.; Huminska-Lisowska, K.; Michałowska-Sawczyn, M.; Homma, H.; Ci˛eszczyk,
P.; Okamoto, T.; Larin, A.K.; et al. Genetic profile of sports climbing athletes from three different ethnicities. Biol. Sport 2022, 39,
913–919. [CrossRef]
66. Kikuchi, N.; Tajima, T.; Tamura, Y.; Yamanaka, Y.; Menuki, K.; Okamoto, T.; Sakamaki-Sunaga, M.; Sakai, A.; Hiranuma, K.;
Nakazato, K. The ALDH2 rs671 polymorphism is associated with athletic status and muscle strength in a Japanese population.
Biol. Sport 2022, 39, 429–434. [CrossRef]
67. De Almeida, K.Y.; Saito, M.; Homma, H.; Mochizuki, Y.; Saito, A.; Deguchi, M.; Kozuma, A.; Okamoto, T.; Nakazato, K.; Kikuchi,
N. ALDH2 gene polymorphism is associated with fitness in the elderly Japanese population. J. Physiol. Anthropol. 2022, 41, 38.
[CrossRef] [PubMed]
68. Saito, A.; Saito, M.; Almeida, K.Y.; Homma, H.; Deguchi, M.; Kozuma, A.; Kobatake, N.; Okamoto, T.; Nakazato, K.; Kikuchi, N.
The Association between the ALDH2 rs671 Polymorphism and Athletic Performance in Japanese Power and Strength Athletes.
Genes 2022, 13, 1735. [CrossRef] [PubMed]
69. Ahmetov, I.I.; Donnikov, A.E.; Trofimov, D.Y. Actn3 genotype is associated with testosterone levels of athletes. Biol. Sport 2014, 31,
105–108. [CrossRef] [PubMed]
70. Baranova, T.I.; Berlov, D.N.; Glotov, O.S.; Korf, E.A.; Minigalin, A.D.; Mitrofanova, A.V.; Ahmetov, I.I.; Glotov, A.S. Genetic
determination of the vascular reactions in humans in response to the diving reflex. Am. J. Physiol. Heart Circ. Physiol. 2017, 312,
H622–H631. [CrossRef] [PubMed]
71. Leońska-Duniec, A.; Ahmetov, I.I.; Zmijewski, P. Genetic variants influencing effectiveness of exercise training programmes in
obesity—an overview of human studies. Biol. Sport 2016, 33, 207–214. [CrossRef]
72. Leońska-Duniec, A.; Jastrz˛ebski, Z.; Jażdżewska, A.; Moska, W.; Lulińska-Kuklik, E.; Sawczuk, M.; Gubaydullina, S.I.; Shakirova,
A.T.; Ci˛eszczyk, P.; Maszczyk, A.; et al. Individual Responsiveness to Exercise-Induced Fat Loss and Improvement of Metabolic
Profile in Young Women is Associated with Polymorphisms of Adrenergic Receptor Genes. J. Sport. Sci. Med. 2018, 17, 134–144.
73. Leonska-Duniec, A.; Ci˛eszczyk, P.; Ahmetov, I.I. Genes and individual responsiveness to exercise-induced fat loss. In Sports,
Exercise, and Nutritional Genomics: Current Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge,
MA, USA, 2019; pp. 231–247. [CrossRef]
74. Massidda, M.; Miyamoto, N.; Beckley, S.; Kikuchi, N.; Fuku, N. Genetics of flexibility. In Sports, Exercise, and Nutritional Genomics:
Current Status and Future Directions; Barh, D., Ahmetov, I., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 273–293.
[CrossRef]
75. Peplonska, B.; Safranow, K.; Adamczyk, J.; Boguszewski, D.; Szymański, K.; Soltyszewski, I.; Barczak, A.; Siewierski, M.; Ploski,
R.; Sozanski, H.; et al. Association of serotoninergic pathway gene variants with elite athletic status in the Polish population.
J. Sport. Sci. 2019, 37, 1655–1662. [CrossRef]
76. Yusof, H.A.; Aziz, A.R.; Muhamed, A.M.C. The influence of angiotensin I-converting enzyme (ACE) I/D gene polymorphism on
cardiovascular and muscular adaptations following 8 weeks of isometric handgrip training (IHG) in untrained normotensive
males. Biol. Sport 2019, 36, 81–94. [CrossRef]
77. Mazur, I.I.; Drozdovska, S.; Andrieieva, O.; Vinnichuk, Y.; Polishchuk, A.; Dosenko, V.; Andreev, I.; Pickering, C.; Ahmetov, I.I.
PPARGC1A gene polymorphism is associated with exercise-induced fat loss. Mol. Biol. Rep. 2020, 47, 7451–7457. [CrossRef]
78. Zhao, Y.; Huang, G.; Chen, Z.; Fan, X.; Huang, T.; Liu, J.; Zhang, Q.; Shen, J.; Li, Z.; Shi, Y. Four Loci Are Associated with
Cardiorespiratory Fitness and Endurance Performance in Young Chinese Females. Sci. Rep. 2020, 10, 10117. [CrossRef]
79. Mountford, H.S.; Hill, A.; Barnett, A.L.; Newbury, D.F. Genome-Wide Association Study of Motor Coordination. Front. Hum.
Neurosci. 2021, 15, 669902. [CrossRef]
80. Williams, C.J.; Li, Z.; Harvey, N.; Lea, R.A.; Gurd, B.J.; Bonafiglia, J.T.; Papadimitriou, I.; Jacques, M.; Croci, I.; Stensvold, D.; et al.
Genome wide association study of response to interval and continuous exercise training: The Predict-HIIT study. J. Biomed. Sci.
2021, 28, 37. [CrossRef]
81. Klevjer, M.; Nordeidet, A.N.; Hansen, A.F.; Madssen, E.; Wisløff, U.; Brumpton, B.M.; Bye, A. Genome-Wide Association Study
Identifies New Genetic Determinants of Cardiorespiratory Fitness: The Trøndelag Health Study. Med. Sci. Sport. Exerc. 2022, 54,
1534–1545. [CrossRef]
82. Bojarczuk, A.; Boulygina, E.A.; Dzitkowska-Zabielska, M.; Łubkowska, B.; Leońska-Duniec, A.; Egorova, E.S.; Semenova, E.A.;
Andryushchenko, L.B.; Larin, A.K.; Generozov, E.V.; et al. Genome-Wide Association Study of Exercise-Induced Fat Loss
Efficiency. Genes 2022, 13, 1975. [CrossRef]
83. McAuley, A.B.T.; Hughes, D.C.; Tsaprouni, L.G.; Varley, I.; Suraci, B.; Baker, J.; Herbert, A.J.; Kelly, A.L. Genetic associations with
personality and mental toughness profiles of English academy football players: An exploratory study. Psychol. Sport Exerc. 2022,
61, 102209. [CrossRef]
Genes 2023, 14, 1235 22 of 32

84. McAuley, A.B.; Hughes, D.C.; Tsaprouni, L.G.; Varley, I.; Suraci, B.; Baker, J.; Herbert, A.J.; Kelly, A.L. Genetic associations with
technical capabilities in English academy football players: A preliminary study. J. Sport. Med. Phys. Fitness 2023, 63, 230–240.
[CrossRef]
85. Tartar, J.L.; Cabrera, D.; Knafo, S.; Thomas, J.D.; Antonio, J.; Peacock, C.A. The “Warrior” COMT Val/Met Genotype Occurs in
Greater Frequencies in Mixed Martial Arts Fighters Relative to Controls. J. Sport. Sci. Med. 2020, 19, 38–42.
86. Ahmetov, I.I.; Valeeva, E.V.; Yerdenova, M.B.; Datkhabayeva, G.K.; Bouzid, A.; Bhamidimarri, P.M.; Sharafetdinova, L.M.;
Egorova, E.S.; Semenova, E.A.; Gabdrakhmanova, L.J.; et al. KIBRA Gene Variant Is Associated with Ability in Chess and Science.
Genes 2023, 14, 204. [CrossRef]
87. Womack, C.J.; Saunders, M.J.; Bechtel, M.K.; Bolton, D.J.; Martin, M.; Luden, N.D.; Dunham, W.; Hancock, M. The influence of a
CYP1A2 polymorphism on the ergogenic effects of caffeine. J. Int. Soc. Sport. Nutr. 2012, 9, 7. [CrossRef]
88. Guest, N.S.; Horne, J.; Vanderhout, S.M.; El-Sohemy, A. Sport Nutrigenomics: Personalized Nutrition for Athletic Performance.
Front. Nutr. 2019, 6, 8. [CrossRef]
89. Guest, N.; Corey, P.; Vescovi, J.; El-Sohemy, A. Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes. Med. Sci.
Sport. Exerc. 2018, 50, 1570–1578. [CrossRef] [PubMed]
90. Guest, N.S.; Corey, P.; Tyrrell, P.N.; El-Sohemy, A. Effect of Caffeine on Endurance Performance in Athletes May Depend on
HTR2A and CYP1A2 Genotypes. J. Strength Cond. Res. 2022, 36, 2486–2492. [CrossRef] [PubMed]
91. Muñoz, A.; López-Samanes, Á.; Aguilar-Navarro, M.; Varillas-Delgado, D.; Rivilla-García, J.; Moreno-Pérez, V.; Del Coso, J.
Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players. Genes
2020, 11, 933. [CrossRef] [PubMed]
92. Wong, O.; Marshall, K.; Sicova, M.; Guest, N.S.; García-Bailo, B.; El-Sohemy, A. CYP1A2 Genotype Modifies the Effects of Caffeine
Compared With Placebo on Muscle Strength in Competitive Male Athletes. Int. J. Sport Nutr. Exerc. Metab. 2021, 31, 420–426.
[CrossRef]
93. Sicova, M.; Guest, N.S.; Tyrrell, P.N.; El-Sohemy, A. Caffeine, genetic variation and anaerobic performance in male athletes: A
randomized controlled trial. Eur. J. Appl. Physiol. 2021, 121, 3499–3513. [CrossRef]
94. Hall, E.C.R.; Semenova, E.A.; Bondareva, E.A.; Andryushchenko, L.B.; Larin, A.K.; Ci˛eszczyk, P.; Generozov, E.V.; Ahmetov, I.I.
Association of Genetically Predicted BCAA Levels with Muscle Fiber Size in Athletes Consuming Protein. Genes 2022, 13, 397.
[CrossRef]
95. Rahimi, R. The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: A randomized,
double-blind, placebo-controlled, crossover study. Ir. J. Med. Sci. 2019, 188, 337–345. [CrossRef]
96. Loy, B.D.; O’Connor, P.J.; Lindheimer, J.B.; Covert, S.F. Caffeine is ergogenic for adenosine A2A receptor gene (ADORA2A) T
allele homozygotes: A pilot study. J. Caffeine Res. 2015, 5, 73–81. [CrossRef]
97. Pickering, C.; Kiely, J. Are the current guidelines on caffeine use in sport optimal for everyone? Inter-individual variation in
caffeine ergogenicity, and a move towards personalised sports nutrition. Sport. Med. 2018, 48, 7–16. [CrossRef]
98. Thomas, R.; Algrain, H.; Ryan, E.; Popojas, A.; Carrigan, P.; Abdulrahman, A.; Carrillo, A. Influence of a CYP1A2 polymorphism
on post-exercise heart rate variability in response to caffeine intake: A double-blind, placebo-controlled trial. Ir. J. Med. Sci. 2017,
186, 285–291. [CrossRef]
99. Rahimi, M.R.; Semenova, E.A.; Larin, A.K.; Kulemin, N.A.; Generozov, E.V.; Łubkowska, B.; Ahmetov, I.I.; Golpasandi, H.
The ADORA2A TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and
Habitual Coffee Intake. Nutrients 2023, 15, 1634. [CrossRef]
100. Guntoro, A.Y.; Melita, S.; Dijaya, R.; Subali, D.; Kartawidjajaputra, F.; Suwanto, A. Evaluation of Caffeine Ingested Timing on
Endurance Performance based on CYP1A2 rs762551 Profiling in Healthy Sedentary Young Adults. Rep. Biochem. Mol. Biol. 2023,
11, 663–671. [CrossRef]
101. Rahim, M.; Collins, M.; September, A. Genes and Musculoskeletal Soft-Tissue Injuries. Med. Sport Sci. 2016, 61, 68–91. [CrossRef]
102. Kim, S.K.; Roche, M.D.; Fredericson, M.; Dragoo, J.L.; Horton, B.H.; Avins, A.L.; Belanger, H.G.; Ioannidis, J.P.A.; Abrams, G.D. A
Genome-wide Association Study for Concussion Risk. Med. Sci. Sport. Exerc. 2021, 53, 704–711. [CrossRef]
103. Lim, T.; Santiago, C.; Pareja-Galeano, H.; Iturriaga, T.; Sosa-Pedreschi, A.; Fuku, N.; Pérez-Ruiz, M.; Yvert, T. Genetic variations
associated with non-contact muscle injuries in sport: A systematic review. Scand. J. Med. Sci. Sport. 2021, 31, 2014–2032. [CrossRef]
104. Antrobus, M.R.; Brazier, J.; Stebbings, G.K.; Day, S.H.; Heffernan, S.M.; Kilduff, L.P.; Erskine, R.M.; Williams, A.G. Genetic Factors
That Could Affect Concussion Risk in Elite Rugby. Sports 2021, 9, 19. [CrossRef]
105. Brazier, J.; Antrobus, M.R.; Herbert, A.J.; Callus, P.C.; Khanal, P.; Stebbings, G.K.; Day, S.H.; Heffernan, S.M.; Kilduff, L.P.; Bennett,
M.A.; et al. Gene variants previously associated with reduced soft-tissue injury risk: Part 2—Polygenic associations with elite
status in Rugby. Eur. J. Sport Sci. 2022, 26, 1–10. [CrossRef]
106. Brazier, J.; Antrobus, M.R.; Herbert, A.J.; Callus, P.C.; Stebbings, G.K.; Day, S.H.; Heffernan, S.M.; Kilduff, L.P.; Bennett, M.A.;
Erskine, R.M.; et al. Gene variants previously associated with reduced soft tissue injury risk: Part 1—independent associations
with elite status in rugby. Eur. J. Sport Sci. 2022, 29, 1–10. [CrossRef]
107. de Almeida, K.Y.; Cetolin, T.; Marrero, A.R.; Aguiar Junior, A.S.; Mohr, P.; Kikuchi, N. A Pilot Study on the Prediction of
Non-Contact Muscle Injuries Based on ACTN3 R577X and ACE I/D Polymorphisms in Professional Soccer Athletes. Genes 2022,
13, 2009. [CrossRef]
Genes 2023, 14, 1235 23 of 32

108. Ginevičienė, V.; Urnikytė, A. Association of COL12A1 rs970547 Polymorphism with Elite Athlete Status. Biomedicines 2022, 10, 2495.
[CrossRef]
109. Jacob, Y.; Anderton, R.S.; Cochrane Wilkie, J.L.; Rogalski, B.; Laws, S.M.; Jones, A.; Spiteri, T.; Hince, D.; Hart, N.H. Genetic
Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian
Football League Players: A Preliminary Study. Sport. Med. Open 2022, 8, 126. [CrossRef] [PubMed]
110. Antrobus, M.R.; Brazier, J.; Callus, P.C.; Herbert, A.J.; Stebbings, G.K.; Khanal, P.; Day, S.H.; Kilduff, L.P.; Bennett, M.A.; Erskine,
R.M.; et al. Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes. Genes 2022, 13, 820. [CrossRef]
111. Hall, E.C.R.; Baumert, P.; Larruskain, J.; Gil, S.M.; Lekue, J.A.; Rienzi, E.; Moreno, S.; Tannure, M.; Murtagh, C.F.; Ade, J.D.; et al.
The genetic association with injury risk in male academy soccer players depends on maturity status. Scand. J. Med. Sci. Sport.
2022, 32, 338–350. [CrossRef] [PubMed]
112. Kumagai, H.; Miyamoto-Mikami, E.; Kikuchi, N.; Kamiya, N.; Zempo, H.; Fuku, N. A rs936306 C/T Polymorphism in the
CYP19A1 Is Associated with Stress Fractures. J. Strength Cond. Res. 2022, 36, 2322–2325. [CrossRef] [PubMed]
113. Varillas-Delgado, D.; Morencos, E.; Gutierrez-Hellín, J.; Aguilar-Navarro, M.; Maestro, A.; Perucho, T.; Coso, J.D. Association of
the CKM rs8111989 Polymorphism with Injury Epidemiology in Football Players. Int. J. Sport. Med. 2023, 44, 145–152. [CrossRef]
114. Varillas-Delgado, D.; Gutierrez-Hellín, J.; Maestro, A. Genetic Profile in Genes Associated with Sports Injuries in Elite Endurance
Athletes. Int. J. Sport. Med. 2023, 44, 64–71. [CrossRef]
115. Ahmetov, I.I.; Hall, E.C.R.; Semenova, E.A.; Pranckevičienė, E.; Ginevičienė, V. Advances in sports genomics. Adv. Clin. Chem.
2022, 107, 215–263. [CrossRef]
116. Egorova, E.S.; Borisova, A.V.; Mustafina, L.J.; Arkhipova, A.A.; Gabbasov, R.T.; Druzhevskaya, A.M.; Astratenkova, I.V.; Ahmetov,
I.I. The polygenic profile of Russian football players. J. Sport. Sci. 2014, 32, 1286–1293. [CrossRef]
117. Youn, B.Y.; Ko, S.G.; Kim, J.Y. Genetic basis of elite combat sports athletes: A systematic review. Biol. Sport 2021, 38, 667–675.
[CrossRef]
118. Abernethy, P.J.; Thayer, R.; Taylor, A.W. Acute and chronic responses of skeletal muscle to endurance and sprint exercise. A
review. Sports Med. 1990, 10, 365–389. [CrossRef]
119. Simoneau, J.A.; Bouchard, C. Genetic determinism of fiber type proportion in human skeletal muscle. FASEB J. 1995, 9, 1091–1095.
[CrossRef]
120. Bassett, D.R., Jr.; Howley, E.T. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med.
Sci. Sport. Exerc. 2000, 32, 70–84. [CrossRef]
121. Ahmetov, I.I.; Vinogradova, O.L.; Williams, A.G. Gene polymorphisms and fiber-type composition of human skeletal muscle. Int.
J. Sport Nutr. Exerc. Metab. 2012, 22, 292–303. [CrossRef]
122. Malczewska-Lenczowska, J.; Orysiak, J.; Majorczyk, E.; Zdanowicz, R.; Szczepańska, B.; Starczewski, M.; Kaczmarski, J.; Dybek,
T.; Pokrywka, A.; Ahmetov, I.I.; et al. Total Hemoglobin Mass, Aerobic Capacity, and HBB Gene in Polish Road Cyclists. J. Strength
Cond. Res. 2016, 30, 3512–3519. [CrossRef]
123. Semenova, E.A.; Khabibova, S.A.; Borisov, O.V.; Generozov, E.V.; Ahmetov, I.I. The Variability of DNA Structure and Muscle-Fiber
Composition. Hum. Physiol. 2019, 45, pp. 225–232. [CrossRef]
124. Konopka, M.J.; Zeegers, M.P.; Solberg, P.A.; Delhaije, L.; Meeusen, R.; Ruigrok, G.; Rietjens, G.; Sperlich, B. Factors associated
with high-level endurance performance: An expert consensus derived via the Delphi technique. PLoS ONE 2022, 17, e0279492.
[CrossRef]
125. Miyamoto-Mikami, E.; Zempo, H.; Fuku, N.; Kikuchi, N.; Miyachi, M.; Murakami, H. Heritability estimates of endurance-related
phenotypes: A systematic review and meta-analysis. Scand. J. Med. Sci. Sport. 2018, 28, 834–845. [CrossRef]
126. Ahmetov, I.I.; Fedotovskaya, O.N. Current Progress in Sports Genomics. Adv. Clin. Chem. 2015, 70, 247–314. [CrossRef]
127. Ahmetov, I.I.; Egorova, E.S.; Gabdrakhmanova, L.J.; Fedotovskaya, O.N. Genes and Athletic Performance: An Update. Med. Sport
Sci. 2016, 61, 41–54. [CrossRef]
128. Myerson, S.; Hemingway, H.; Budget, R.; Martin, J.; Humphries, S.; Montgomery, H. Human angiotensin I-converting enzyme
gene and endurance performance. J. Appl. Physiol. 1999, 87, 1313–1316. [CrossRef]
129. Jelakovic, B.; Kuzmanic, D.; Milicic, D. Influence of angiotensin converting enzyme (ACE) gene polymorphism and circadian
blood pressure (BP) changes on left ventricle (LV) mass in competitive oarsmen. Am. J. Hypertens. 2000, 13, 182A. [CrossRef]
130. Ahmetov, I.I.; Popov, D.V.; Astratenkova, I.V.; Druzhevskaia, A.M.; Missina, S.S.; Vinogradova, O.L.; Rogozkin, V.A. The use
of molecular genetic methods for prognosis of aerobic and anaerobic performance in athletes. Hum. Physiol. 2008, 34, 338–342.
[CrossRef]
131. Alvarez, R.; Terrados, N.; Ortolano, R.; Iglesias-Cubero, G.; Reguero, J.R.; Batalla, A.; Cortina, A.; Fernández-García, B.; Rodríguez,
C.; Braga, S.; et al. Genetic variation in the renin-angiotensin system and athletic performance. Eur. J. Appl. Physiol. 2000, 82,
117–120. [CrossRef] [PubMed]
132. Collins, M.; Xenophontos, S.L.; Cariolou, M.A.; Mokone, G.G.; Hudson, D.E.; Anastasiades, L.; Noakes, T.D. The ACE gene and
endurance performance during the South African Ironman Triathlons. Med. Sci. Sport. Exerc. 2004, 36, 1314–1320. [CrossRef]
[PubMed]
133. Lucía, A.; Gómez-Gallego, F.; Chicharro, J.L.; Hoyos, J.; Celaya, K.; Córdova, A.; Villa, G.; Alonso, J.M.; Barriopedro, M.; Pérez,
M.; et al. Is there an association between ACE and CKMM polymorphisms and cycling performance status during 3-week races?
Int. J. Sport. Med. 2005, 26, 442–447. [CrossRef]
Genes 2023, 14, 1235 24 of 32

134. Hruskovicová, H.; Dzurenková, D.; Selingerová, M.; Bohus, B.; Timkanicová, B.; Kovács, L. The angiotensin converting enzyme
I/D polymorphism in long distance runners. J. Sports Med. Phys. Fitness 2006, 46, 509–513.
135. Scanavini, D.; Bernardi, F.; Castoldi, E.; Conconi, F.; Mazzoni, G. Increased frequency of the homozygous II ACE genotype in
Italian Olympic endurance athletes. Eur. J. Hum. Genet. 2002, 10, 576–577. [CrossRef]
136. Turgut, G.; Turgut, S.; Genc, O.; Atalay, A.; Atalay, E.O. The angiotensin converting enzyme I/D polymorphism in Turkish
athletes and sedentary controls. Acta Med. 2004, 47, 133–136. [CrossRef]
137. Tsianos, G.; Sanders, J.; Dhamrait, S.; Humphries, S.; Grant, S.; Montgomery, H. The ACE gene insertion/deletion polymorphism
and elite endurance swimming. Eur. J. Appl. Physiol. 2004, 92, 360–362. [CrossRef]
138. Cieszczyk, P.; Krupecki, K.; Maciejewska, A.; Sawczuk, M. The angiotensin converting enzyme gene I/D polymorphism in Polish
rowers. Int. J. Sport. Med. 2009, 30, 624–627. [CrossRef]
139. Min, S.K.; Takahashi, K.; Ishigami, H.; Hiranuma, K.; Mizuno, M.; Ishii, T.; Kim, C.S.; Nakazato, K. Is there a gender difference
between ACE gene and race distance? Appl. Physiol. Nutr. Metab. 2009, 34, 926–932. [CrossRef]
140. Shenoy, S.; Tandon, S.; Sandhu, J.; Bhanwer, A.S. Association of Angiotensin Converting Enzyme gene Polymorphism and Indian
Army Triathletes Performance. Asian J. Sport. Med. 2010, 1, 143–150. [CrossRef]
141. Znazen, H.; Mejri, A.; Touhami, I.; Chtara, M.; Siala, H.; LE Gallais, D.; Ahmetov, I.I.; Messaoud, T.; Chamari, K.; Soussi, N.
Genetic advantageous predisposition of angiotensin converting enzyme id polymorphism in Tunisian athletes. J. Sport. Med.
Phys. Fit. 2016, 56, 724–730.
142. Ash, G.I.; Scott, R.A.; Deason, M.; Dawson, T.A.; Wolde, B.; Bekele, Z.; Teka, S.; Pitsiladis, Y.P. No association between ACE gene
variation and endurance athlete status in Ethiopians. Med. Sci. Sport. Exerc. 2011, 43, 590–597. [CrossRef]
143. Tobina, T.; Michishita, R.; Yamasawa, F.; Zhang, B.; Sasaki, H.; Tanaka, H.; Saku, K.; Kiyonaga, A. Association between the
angiotensin I-converting enzyme gene insertion/deletion polymorphism and endurance running speed in Japanese runners. J.
Physiol. Sci. 2010, 60, 325–330. [CrossRef]
144. Ahmetov, I.I.; Williams, A.G.; Popov, D.V.; Lyubaeva, E.V.; Hakimullina, A.M.; Fedotovskaya, O.N.; Mozhayskaya, I.A.;
Vinogradova, O.L.; Astratenkova, I.V.; Montgomery, H.E.; et al. The combined impact of metabolic gene polymorphisms
on elite endurance athlete status and related phenotypes. Hum. Genet. 2009, 126, 751–761. [CrossRef]
145. Papadimitriou, I.D.; Papadopoulos, C.; Kouvatsi, A.; Triantaphyllidis, C. The ACE I/D polymorphism in elite Greek track and
field athletes. J. Sport. Med. Phys. Fit. 2009, 49, 459–463.
146. Scott, R.A.; Moran, C.; Wilson, R.H.; Onywera, V.; Boit, M.K.; Goodwin, W.H.; Gohlke, P.; Payne, J.; Montgomery, H.; Pitsiladis,
Y.P. No association between Angiotensin Converting Enzyme (ACE) gene variation and endurance athlete status in Kenyans.
Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2005, 141, 169–175. [CrossRef]
147. Rankinen, T.; Wolfarth, B.; Simoneau, J.A.; Maier-Lenz, D.; Rauramaa, R.; Rivera, M.A.; Boulay, M.R.; Chagnon, Y.C.; Pérusse, L.;
Keul, J.; et al. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status.
J. Appl. Physiol. 2000, 88, 1571–1575. [CrossRef]
148. Taylor, R.R.; Mamotte, C.D.; Fallon, K.; van Bockxmeer, F.M. Elite athletes and the gene for angiotensin-converting enzyme.
J. Appl. Physiol. 1999, 87, 1035–1037. [CrossRef]
149. Orysiak, J.; Zmijewski, P.; Klusiewicz, A.; Kaliszewski, P.; Malczewska-Lenczowska, J.; Gajewski, J.; Pokrywka, A. The association
between ace gene variation and aerobic capacity in winter endurance disciplines. Biol. Sport 2013, 30, 249–253. [CrossRef]
[PubMed]
150. Ginevičienė, V.; Pranculis, A.; Jakaitienė, A.; Milašius, K.; Kučinskas, V. Genetic variation of the human ACE and ACTN3 genes
and their association with functional muscle properties in Lithuanian elite athletes. Medicina 2011, 47, 40. [CrossRef] [PubMed]
151. Muniesa, C.A.; González-Freire, M.; Santiago, C.; Lao, J.I.; Buxens, A.; Rubio, J.C.; Martín, M.A.; Arenas, J.; Gomez-Gallego, F.;
Lucia, A. World-class performance in lightweight rowing: Is it genetically influenced? A comparison with cyclists, runners and
non-athletes. Br. J. Sport. Med. 2010, 44, 898–901. [CrossRef] [PubMed]
152. Papadimitriou, I.D.; Lockey, S.J.; Voisin, S.; Herbert, A.J.; Garton, F.; Houweling, P.J.; Cieszczyk, P.; Maciejewska-Skrendo, A.;
Sawczuk, M.; Massidda, M.; et al. No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running
times in 698 Caucasian athletes. BMC Genomics 2018, 19, 13. [CrossRef] [PubMed]
153. Varillas-Delgado, D.; Morencos, E.; Gutiérrez-Hellín, J.; Aguilar-Navarro, M.; Muñoz, A.; Mendoza Láiz, N.; Perucho, T.; Maestro,
A.; Tellería-Orriols, J.J. Genetic profiles to identify talents in elite endurance athletes and professional football players. PLoS ONE
2022, 17, e0274880. [CrossRef]
154. Shang, X.; Huang, C.; Chang, Q.; Zhang, L.; Huang, T. Association between the ACTN3 R577X polymorphism and female
endurance athletes in China. Int. J. Sport. Med. 2010, 31, 913–916. [CrossRef]
155. Gasser, B.; Flück, M.; Frey, W.O.; Valdivieso, P.; Spörri, J. Association of Gene Variants for Mechanical and Metabolic Muscle
Quality with Cardiorespiratory and Muscular Variables Related to Performance in Skiing Athletes. Genes 2022, 13, 1798. [CrossRef]
156. Orysiak, J.; Sitkowski, D.; Zmijewski, P.; Malczewska-Lenczowska, J.; Cieszczyk, P.; Zembron-Lacny, A.; Pokrywka, A. Over-
representation of the ACTN3 XX genotype in elite canoe and kayak paddlers. J. Strength Cond. Res. 2015, 29, 1107–1112.
[CrossRef]
157. Ahmetov, I.I.; Druzhevskaya, A.M.; Astratenkova, I.V.; Popov, D.V.; Vinogradova, O.L.; Rogozkin, V.A. The ACTN3 R577X
polymorphism in Russian endurance athletes. Br. J. Sport. Med. 2010, 44, 649–652. [CrossRef]
Genes 2023, 14, 1235 25 of 32

158. Döring, F.E.; Onur, S.; Geisen, U.; Boulay, M.R.; Pérusse, L.; Rankinen, T.; Rauramaa, R.; Wolfahrt, B.; Bouchard, C. ACTN3 R577X
and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study. J. Sport. Sci. 2010, 28,
1355–1359. [CrossRef]
159. Ginevičienė, V.; Pranckevičienė, E.; Milašius, K.; Kučinskas, V. Relating fitness phenotypes to genotypes in Lithuanian elite
athletes. Acta Med. Litu. 2010, 17, 1–10. [CrossRef]
160. Tsianos, G.I.; Evangelou, E.; Boot, A.; Zillikens, M.C.; van Meurs, J.B.; Uitterlinden, A.G.; Ioannidis, J.P. Associations of
polymorphisms of eight muscle- or metabolism-related genes with performance in Mount Olympus marathon runners. J. Appl.
Physiol. 2010, 108, 567–574. [CrossRef]
161. Niemi, A.K.; Majamaa, K. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur. J. Hum.
Genet. 2005, 13, 965–969. [CrossRef]
162. Papadimitriou, I.D.; Papadopoulos, C.; Kouvatsi, A.; Triantaphyllidis, C. The ACTN3 gene in elite Greek track and field athletes.
Int. J. Sport. Med. 2008, 29, 352–355. [CrossRef]
163. Paparini, A.; Ripani, M.; Giordano, G.D.; Santoni, D.; Pigozzi, F.; Romano-Spica, V. ACTN3 genotyping by real-time PCR in the
Italian population and athletes. Med. Sci. Sport. Exerc. 2007, 39, 810–815. [CrossRef]
164. Saunders, C.J.; September, A.V.; Xenophontos, S.L.; Cariolou, M.A.; Anastassiades, L.C.; Noakes, T.D.; Collins, M. No association
of the ACTN3 gene R577X polymorphism with endurance performance in Ironman Triathlons. Ann. Hum. Genet. 2007, 71,
777–781. [CrossRef]
165. Yang, N.; MacArthur, D.G.; Wolde, B.; Onywera, V.O.; Boit, M.K.; Lau, S.Y.; Wilson, R.H.; Scott, R.A.; Pitsiladis, Y.P.; North, K. The
ACTN3 R577X polymorphism in East and West African athletes. Med. Sci. Sports Exerc. 2007, 39, 1985–1988. [CrossRef]
166. Lucia, A.; Gómez-Gallego, F.; Santiago, C.; Bandrés, F.; Earnest, C.; Rabadán, M.; Alonso, J.M.; Hoyos, J.; Córdova, A.; Villa,
G.; et al. ACTN3 genotype in professional endurance cyclists. Int. J. Sports Med. 2006, 27, 880–884. [CrossRef]
167. Grealy, R.; Smith, C.L.; Chen, T.; Hiller, D.; Haseler, L.J.; Griffiths, L.R. The genetics of endurance: Frequency of the ACTN3 R577X
variant in Ironman World Championship athletes. J. Sci. Med. Sport 2013, 16, 365–371. [CrossRef]
168. Mikami, E.; Fuku, N.; Murakami, H.; Tsuchie, H.; Takahashi, H.; Ohiwa, N.; Tanaka, H.; Pitsiladis, Y.P.; Higuchi, M.; Miyachi,
M.; et al. ACTN3 R577X genotype is associated with sprinting in elite Japanese athletes. Int. J. Sport. Med. 2014, 35, 172–177.
[CrossRef]
169. Wang, G.; Mikami, E.; Chiu, L.L.; DE Perini, A.; Deason, M.; Fuku, N.; Miyachi, M.; Kaneoka, K.; Murakami, H.; Tanaka, M.; et al.
Association analysis of ACE and ACTN3 in elite Caucasian and East Asian swimmers. Med. Sci. Sport. Exerc. 2013, 45, 892–900.
[CrossRef] [PubMed]
170. Yang, R.; Jin, F.; Wang, L.; Shen, X.; Guo, Q.; Song, H.; Hu, J.; Zhao, Q.; Wan, J.; Cai, M. Prediction and Identification of Power
Performance Using Polygenic Models of Three Single-Nucleotide Polymorphisms in Chinese Elite Athletes. Front. Genet. 2021, 12,
726552. [CrossRef] [PubMed]
171. Wagoner, L.E.; Craft, L.L.; Singh, B.; Suresh, D.P.; Zengel, P.W.; McGuire, N.; Abraham, W.T.; Chenier, T.C.; Dorn, G.W., 2nd;
Liggett, S.B. Polymorphisms of the β(2)-adrenergic receptor determine exercise capacity in patients with heart failure. Circ. Res.
2000, 86, 834–840. [CrossRef] [PubMed]
172. Wolfarth, B.; Rankinen, T.; Mühlbauer, S.; Scherr, J.; Boulay, M.R.; Pérusse, L.; Rauramaa, R.; Bouchard, C. Association between a
beta2-adrenergic receptor polymorphism and elite endurance performance. Metabolism 2007, 56, 1649–1651. [CrossRef] [PubMed]
173. Santiago, C.; Ruiz, J.R.; Buxens, A.; Artieda, M.; Arteta, D.; González-Freire, M.; Rodríguez-Romo, G.; Altmäe, S.; Lao, J.I.;
Gómez-Gallego, F.; et al. Trp64Arg polymorphism in ADRB3 gene is associated with elite endurance performance. Br. J. Sport.
Med. 2011, 45, 147–149. [CrossRef]
174. Sawczuk, M.; Maciejewska-Karlowska, A.; Cieszczyk, P.; Skotarczak, B.; Ficek, K. Association of the ADRB2 Gly16Arg and
Glu27Gln polymorphisms with athlete status. J. Sports Sci. 2013, 31, 1535–1544. [CrossRef]
175. Moore, G.E.; Shuldiner, A.R.; Zmuda, J.M.; Ferrell, R.E.; McCole, S.D.; Hagberg, J.M. Obesity gene variant and elite endurance
performance. Metabolism 2001, 50, 1391–1392. [CrossRef]
176. Mustafina, L.J.; Naumov, V.A.; Cieszczyk, P.; Popov, D.V.; Lyubaeva, E.V.; Kostryukova, E.S.; Fedotovskaya, O.N.; Druzhevskaya,
A.M.; Astratenkova, I.V.; Glotov, A.S.; et al. AGTR2 gene polymorphism is associated with muscle fibre composition, athletic
status and aerobic performance. Exp. Physiol. 2014, 99, 1042–1052. [CrossRef]
177. Guilherme, J.P.L.F.; Silva, M.S.; Bertuzzi, R.; Lancha Junior, A.H. The AGTR2 rs11091046 (A>C) polymorphism and power athletic
status in top-level Brazilian athletes. J. Sport. Sci. 2018, 36, 2327–2332. [CrossRef]
178. Martínez, J.L.; Carrión, A.; Florián, M.E.; Martín, J.A.; López-Taylor, J.R.; Fahey, T.D.; Rivera, M.A. Aquaporin-1 gene DNA
variation predicts performance in Hispanic marathon runners. Med. Sport 2009, 13, 251–255. [CrossRef]
179. Rivera, M.A.; Martínez, J.L.; Carrion, A.; Fahey, T.D. AQP-1 association with body fluid loss in 10-km runners. Int. J. Sport. Med.
2011, 32, 229–233. [CrossRef]
180. Saunders, C.J.; Posthumus, M.; O’Connell, K.; September, A.V.; Collins, M. A variant within the AQP1 30 -untranslated region is
associated with running performance, but not weight changes, during an Ironman Triathlon. J. Sports Sci. 2015, 33, 1342–1348.
[CrossRef]
181. Rico-Sanz, J.; Rankinen, T.; Joanisse, D.R.; Leon, A.S.; Skinner, J.S.; Wilmore, J.H.; Rao, D.C.; Bouchard, C.; HERITAGE Family
study. Associations between cardiorespiratory responses to exercise and the C34T AMPD1 gene polymorphism in the HERITAGE
Family Study. Physiol. Genom. 2003, 14, 161–166. [CrossRef]
Genes 2023, 14, 1235 26 of 32

182. Thomaes, T.; Thomis, M.; Onkelinx, S.; Fagard, R.; Matthijs, G.; Buys, R.; Schepers, D.; Cornelissen, V.; Vanhees, L. A genetic
predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: The CAREGENE study.
BMC Genet. 2011, 12, 84. [CrossRef]
183. Ciȩszczyk, P.; Eider, J.; Ostanek, M.; Leońska-Duniec, A.; Ficek, K.; Kotarska, K.; Girdauskas, G. Is the C34T polymorphism of the
AMPD1 gene associated with athlete performance in rowing? Int. J. Sport. Med. 2011, 32, 987–991. [CrossRef]
184. Ginevičienė, V.; Jakaitienė, A.; Pranculis, A.; Milašius, K.; Tubelis, L.; Utkus, A. AMPD1 rs17602729 is associated with physical
performance of sprint and power in elite Lithuanian athletes. BMC Genet. 2014, 15, 58. [CrossRef]
185. Williams, A.G.; Dhamrait, S.S.; Wootton, P.T.; Day, S.H.; Hawe, E.; Payne, J.R.; Myerson, S.G.; World, M.; Budgett, R.; Humphries,
S.E.; et al. Bradykinin receptor gene variant and human physical performance. J. Appl. Physiol. 2004, 96, 938–942. [CrossRef]
186. Saunders, C.J.; Xenophontos, S.L.; Cariolou, M.A.; Anastassiades, L.C.; Noakes, T.D.; Collins, M. The bradykinin β 2 receptor
(BDKRB2) and endothelial nitric oxide synthase 3 (NOS3) genes and endurance performance during Ironman Triathlons. Hum.
Mol. Genet. 2006, 15, 979–987. [CrossRef]
187. Sawczuk, M.; Timshina, Y.I.; Astratenkova, I.V.; Maciejewska-Karlowska, A.; Leońska-Duniec, A.; Ficek, K.; Mustafina, L.J.;
Ci˛eszczyk, P.; Klocek, T.; Ahmetov, I.I. The −9/+9 polymorphism of the bradykinin receptor β 2 gene and athlete status: A study
involving two European cohorts. Hum. Biol. 2013, 85, 741–756. [CrossRef]
188. Grenda, A.; Leońska-Duniec, A.; Ci˛eszczyk, P.; Zmijewski, P. Bdkrb2 gene -9/+9 polymorphism and swimming performance.
Biol. Sport 2014, 31, 109–113. [CrossRef]
189. Zmijewski, P.; Grenda, A.; Leońska-Duniec, A.; Ahmetov, I.; Orysiak, J.; Ci˛eszczyk, P. Effect of BDKRB2 Gene -9/+9 Polymorphism
on Training Improvements in Competitive Swimmers. J. Strength Cond. Res. 2016, 30, 665–671. [CrossRef] [PubMed]
190. Rivera, M.A.; Dionne, F.T.; Simoneau, J.A.; Pérusse, L.; Chagnon, M.; Chagnon, Y.; Gagnon, J.; Leon, A.S.; Rao, D.C.; Skinner,
J.S.; et al. Muscle-specific creatine kinase gene polymorphism and VO2max in the HERITAGE Family Study. Med. Sci. Sport.
Exerc. 1997, 29, 1311–1317. [CrossRef] [PubMed]
191. Rivera, M.A.; Pérusse, L.; Simoneau, J.A.; Gagnon, J.; Dionne, F.T.; Leon, A.S.; Skinner, J.S.; Wilmore, J.H.; Province, M.; Rao, D.C.;
et al. Linkage between a muscle-specific CK gene marker and VO2max in the HERITAGE Family Study. Med. Sci. Sport. Exerc.
1999, 31, 698–701. [CrossRef] [PubMed]
192. Fedotovskaya, O.N.; Popov, D.V.; Vinogradova, O.L.; Akhmetov, I.I. Association of muscle-specific creatine kinase (CKMM) gene
polymorphism with physical performance of athletes. Hum. Physiol. 2012, 38, 89–93. [CrossRef]
193. Martínez, J.L.; Khorsandi, S.; Sojo, R.; Martínez, C.; Martín, J.A.; López-Taylor, J.R.; Fahey, T.D.; Rivera, M.A. Lack of an
Association Between CKMM Genotype and Endurance Performance Level in Hispanic Marathon Runners. Med. Sport 2009, 13,
219–223. [CrossRef]
194. Posthumus, M.; Schwellnus, M.P.; Collins, M. The COL5A1 gene: A novel marker of endurance running performance. Med. Sci.
Sport. Exerc. 2011, 43, 584–589. [CrossRef]
195. Brown, J.C.; Miller, C.J.; Posthumus, M.; Schwellnus, M.P.; Collins, M. The COL5A1 gene, ultra-marathon running performance,
and range of motion. Int. J. Sport. Physiol. Perform. 2011, 6, 485–496. [CrossRef]
196. Guilherme, J.; Egorova, E.S.; Semenova, E.A.; Kostryukova, E.S.; Kulemin, N.A.; Borisov, O.V.; Khabibova, S.A.; Larin, A.K.;
Ospanova, E.A.; Pavlenko, A.V.; et al. The A-allele of the FTO gene rs9939609 polymorphism is associated with decreased
proportion of slow oxidative muscle fibers and over-represented in heavier athletes. J. Strength Cond. Res. 2019, 33, 691–700.
[CrossRef]
197. Zmijewski, P.; Leońska-Duniec, A. Association between the FTO A/T Polymorphism and Elite Athlete Status in Caucasian
Swimmers. Genes 2021, 12, 715. [CrossRef]
198. Eynon, N.; Nasibulina, E.S.; Banting, L.K.; Cieszczyk, P.; Maciejewska-Karlowska, A.; Sawczuk, M.; Bondareva, E.A.; Shagimar-
danova, R.R.; Raz, M.; Sharon, Y.; et al. The FTO A/T polymorphism and elite athletic performance: A study involving three
groups of European athletes. PLoS ONE 2013, 8, e60570. [CrossRef]
199. He, Z.; Hu, Y.; Feng, L.; Lu, Y.; Liu, G.; Xi, Y.; Wen, L.; McNaughton, L.R. NRF2 genotype improves endurance capacity in
response to training. Int. J. Sport. Med. 2007, 28, 717–721. [CrossRef]
200. Eynon, N.; Ruiz, J.R.; Bishop, D.J.; Santiago, C.; Gómez-Gallego, F.; Lucia, A.; Birk, R. The rs12594956 polymorphism in the NRF-2
gene is associated with top-level Spanish athlete’s performance status. J. Sci. Med. Sport 2013, 16, 135–139. [CrossRef]
201. Maciejewska-Karłowska, A.; Leońska-Duniec, A.; Ci˛eszczyk, P.; Sawczuk, M.; Eider, J.; Ficek, K.; Sawczyn, S. The GABPB1 gene
A/G polymorphism in Polish rowers. J. Hum. Kinet. 2012, 31, 115–120. [CrossRef]
202. Zarebska, A.; Jastrzebski, Z.; Kaczmarczyk, M.; Ficek, K.; Maciejewska-Karlowska, A.; Sawczuk, M.; Leońska-Duniec, A.; Krol, P.;
Cieszczyk, P.; Zmijewski, P.; et al. The GSTP1 c.313A>G polymorphism modulates the cardiorespiratory response to aerobic
training. Biol. Sport 2014, 31, 261–266. [CrossRef]
203. Zarebska, A.; Jastrzebski, Z.; Ahmetov, I.I.; Zmijewski, P.; Cieszczyk, P.; Leonska-Duniec, A.; Sawczuk, M.; Leznicka, K.; Trybek,
G.; Semenova, E.A.; et al. GSTP1 c.313A>G polymorphism in Russian and Polish athletes. Physiol. Genom. 2017, 49, 127–131.
[CrossRef]
204. Deugnier, Y.; Loréal, O.; Carré, F.; Duvallet, A.; Zoulim, F.; Vinel, J.P.; Paris, J.C.; Blaison, D.; Moirand, R.; Turlin, B.; et al. Increased
body iron stores in elite road cyclists. Med. Sci. Sport. Exerc. 2002, 34, 876–880. [CrossRef]
Genes 2023, 14, 1235 27 of 32

205. Chicharro, J.L.; Hoyos, J.; Gómez-Gallego, F.; Villa, J.G.; Bandrés, F.; Celaya, P.; Jiménez, F.; Alonso, J.M.; Córdova, A.; Lucia, A.
Mutations in the hereditary haemochromatosis gene HFE in professional endurance athletes. Br. J. Sport. Med. 2004, 38, 418–421.
[CrossRef]
206. Hermine, O.; Dine, G.; Genty, V.; Marquet, L.A.; Fumagalli, G.; Tafflet, M.; Guillem, F.; Van Lierde, F.; Rousseaux-Blanchi, M.P.;
Palierne, C.; et al. Eighty percent of French sport winners in Olympic, World and Europeans competitions have mutations in the
hemochromatosis HFE gene. Biochimie 2015, 119, 1–5. [CrossRef]
207. Semenova, E.A.; Miyamoto-Mikami, E.; Akimov, E.B.; Al-Khelaifi, F.; Murakami, H.; Zempo, H.; Kostryukova, E.S.; Kulemin,
N.A.; Larin, A.K.; Borisov, O.V.; et al. The association of HFE gene H63D polymorphism with endurance athlete status and
aerobic capacity: Novel findings and a meta-analysis. Eur. J. Appl. Physiol. 2020, 120, 665–673. [CrossRef]
208. Prior, S.J.; Hagberg, J.M.; Phares, D.A.; Brown, M.D.; Fairfull, L.; Ferrell, R.E.; Roth, S.M. Sequence variation in hypoxia-inducible
factor 1alpha (HIF1A): Association with maximal oxygen consumption. Physiol. Genom. 2003, 15, 20–26. [CrossRef]
209. Döring, F.; Onur, S.; Fischer, A.; Boulay, M.R.; Pérusse, L.; Rankinen, T.; Rauramaa, R.; Wolfarth, B.; Bouchard, C. A common
haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1alpha (HIF1A) gene in elite endurance athletes.
J. Appl. Physiol. 2010, 108, 1497–1500. [CrossRef] [PubMed]
210. Bosnyák, E.; Trájer, E.; Alszászi, G.; Móra, Á.; Györe, I.; Udvardy, A.; Tóth, M.; Szmodis, M. Lack of association between the GNB3
rs5443, HIF1A rs11549465 polymorphisms, physiological and functional characteristics. Ann. Hum. Genet. 2020, 84, 393–399.
[CrossRef] [PubMed]
211. Merezhinskaya, N.; Fishbein, W.N.; Davis, J.I.; Foellmer, J.W. Mutations in MCT1 cDNA in patients with symptomatic deficiency
in lactate transport. Muscle Nerve 2000, 23, 90–97. [CrossRef]
212. Cupeiro, R.; Benito, P.J.; Maffulli, N.; Calderón, F.J.; González-Lamuño, D. MCT1 genetic polymorphism influence in high intensity
circuit training: A pilot study. J. Sci. Med. Sport 2010, 13, 526–530. [CrossRef]
213. Fedotovskaya, O.N.; Mustafina, L.J.; Popov, D.V.; Vinogradova, O.L.; Ahmetov, I.I. A common polymorphism of the MCT1 gene
and athletic performance. Int. J. Sport. Physiol. Perform. 2014, 9, 173–180. [CrossRef]
214. Ramírez de la Piscina-Viúdez, X.; Álvarez-Herms, J.; Bonilla, D.A.; Castañeda-Babarro, A.; Larruskain, J.; Díaz-Ramírez, J.;
Ahmetov, I.I.; Martínez-Ascensión, A.; Kreider, R.B.; Odriozola-Martínez, A. Putative Role of MCT1 rs1049434 Polymorphism in
High-Intensity Endurance Performance: Concept and Basis to Understand Possible Individualization Stimulus. Sports 2021, 9, 143.
[CrossRef]
215. Sawczuk, M.; Banting, L.K.; Ci˛eszczyk, P.; Maciejewska-Karłowska, A.; Zar˛ebska, A.; Leońska-Duniec, A.; Jastrz˛ebski, Z.; Bishop,
D.J.; Eynon, N. MCT1 A1470T: A novel polymorphism for sprint performance? J. Sci. Med. Sport 2015, 18, 114–118. [CrossRef]
216. Maruszak, A.; Adamczyk, J.G.; Siewierski, M.; Sozański, H.; Gajewski, A.; Żekanowski, C. Mitochondrial DNA variation is
associated with elite athletic status in the Polish population. Scand. J. Med. Sci. Sport. 2014, 24, 311–318. [CrossRef]
217. Drozdovska, S.B.; Dosenko, V.E.; Ilyin, V.N.; Filippov, M.M.; Kuzmina, L.M. Allelic Polymorphism of Endothelial No-Synthase
(eNOS) Association with Exercise-Induced Hypoxia Adaptation. Baltic. J. Health Phys. Activ. 2009, 1, 13–19. [CrossRef]
218. Zmijewski, P.; Ci˛eszczyk, P.; Ahmetov, I.I.; Gronek, P.; Lulińska-Kuklik, E.; Dornowski, M.; Rzeszutko, A.; Chycki, J.; Moska, W.;
Sawczuk, M. The NOS3 G894T (rs1799983) and -786T/C (rs2070744) polymorphisms are associated with elite swimmer status.
Biol. Sport 2018, 35, 313–319. [CrossRef]
219. Gómez-Gallego, F.; Ruiz, J.R.; Buxens, A.; Artieda, M.; Arteta, D.; Santiago, C.; Rodríguez-Romo, G.; Lao, J.I.; Lucia, A. The
-786 T/C polymorphism of the NOS3 gene is associated with elite performance in power sports. Eur. J. Appl. Physiol. 2009, 107,
565–569. [CrossRef]
220. Ahmetov, I.I.; Mozhayskaya, I.A.; Flavell, D.M.; Astratenkova, I.V.; Komkova, A.I.; Lyubaeva, E.V.; Tarakin, P.P.; Shenkman, B.S.;
Vdovina, A.B.; Netreba, A.I.; et al. PPARalpha gene variation and physical performance in Russian athletes. Eur. J. Appl. Physiol.
2006, 97, 103–108. [CrossRef]
221. Maciejewska, A.; Sawczuk, M.; Ci˛eszczyk, P. Variation in the PPARα gene in Polish rowers. J. Sci. Med. Sport 2011, 14, 58–64.
[CrossRef]
222. Tural, E.; Kara, N.; Agaoglu, S.A.; Elbistan, M.; Tasmektepligil, M.Y.; Imamoglu, O. PPAR-α and PPARGC1A gene variants have
strong effects on aerobic performance of Turkish elite endurance athletes. Mol. Biol. Rep. 2014, 41, 5799–5804. [CrossRef]
223. Maciejewska, A.; Sawczuk, M.; Cieszczyk, P.; Mozhayskaya, I.A.; Ahmetov, I.I. The PPARGC1A gene Gly482Ser in Polish and
Russian athletes. J. Sport. Sci. 2012, 30, 101–113. [CrossRef]
224. He, Z.H.; Hu, Y.; Li, Y.C.; Gong, L.J.; Cieszczyk, P.; Maciejewska-Karlowska, A.; Leonska-Duniec, A.; Muniesa, C.A.; Marín-Peiro,
M.; Santiago, C.; et al. PGC-related gene variants and elite endurance athletic status in a Chinese cohort: A functional study.
Scand. J. Med. Sci. Sport. 2015, 25, 184–195. [CrossRef]
225. Hall, E.C.R.; Lockey, S.J.; Heffernan, S.M.; Herbert, A.J.; Stebbings, G.K.; Day, S.H.; Collins, M.; Pitsiladis, Y.P.; Erskine, R.M.;
Williams, A.G. The PPARGC1A Gly482Ser polymorphism is associated with elite long-distance running performance. J. Sport. Sci.
2023, 41, 56–62. [CrossRef]
226. Akhmetov, I.I.; Popov, D.V.; Missina, S.S.; Vinogradova, O.L.; Rogozkin, V.A. The analysis of PPARGC1B gene polymorphism in
athletes. Ross. Fiziol. Zh. Im. I.M. Sechenova 2009, 95, 1247–1253.
227. Akhmetov, I.I.; Linde, E.V.; Shikhova, I.V.; Popov, D.V.; Missina, S.S.; Vinogradoba, O.L.; Rogozkin, V.A. The influence of
calcineurin gene polymorphism on morphofunctional characteristics of cardiovascular system of athletes. Ross. Fiziol. Zh. Im.
I.M. Sechenova 2008, 94, 915–922.
Genes 2023, 14, 1235 28 of 32

228. Bouchard, C.; Sarzynski, M.A.; Rice, T.K.; Kraus, W.E.; Church, T.S.; Sung, Y.J.; Rao, D.C.; Rankinen, T. Genomic predictors of the
maximal O2 uptake response to standardized exercise training programs. J. Appl. Physiol. 2011, 110, 1160–1170. [CrossRef]
229. Hall, E.C.R.; Almeida, S.S.; Heffernan, S.M.; Lockey, S.J.; Herbert, A.J.; Callus, P.; Day, S.H.; Pedlar, C.R.; Kipps, C.; Collins,
M.; et al. Genetic Polymorphisms Related to VO2max Adaptation Are Associated with Elite Rugby Union Status and Competitive
Marathon Performance. Int. J. Sport. Physiol. Perform. 2021, 16, 1858–1864. [CrossRef] [PubMed]
230. Kusić, D.; Connolly, J.; Kainulainen, H.; Semenova, E.A.; Borisov, O.V.; Larin, A.K.; Popov, D.V.; Generozov, E.V.; Ahmetov, I.I.;
Britton, S.L.; et al. Striated muscle-specific serine/threonine-protein kinase β segregates with high versus low responsiveness to
endurance exercise training. Physiol. Genom. 2020, 52, 35–46. [CrossRef] [PubMed]
231. Ahmetov, I.I.; Popov, D.V.; Missina, S.S.; Vinogradova, O.L.; Rogozkin, V.A. Association of mitochondrial transcription factor
(TFAM) gene polymorphism with physical performance in athletes. Hum. Physiol. 2010, 36, 229–233. [CrossRef]
232. Gronek, P.; Gronek, J.; Lulińska-Kuklik, E.; Spieszny, M.; Niewczas, M.; Kaczmarczyk, M.; Petr, M.; Fischerova, P.; Ahmetov, I.I.;
Żmijewski, P. Polygenic Study of Endurance-Associated Genetic Markers NOS3 (Glu298Asp), BDKRB2 (-9/+9), UCP2 (Ala55Val),
AMPD1 (Gln45Ter) and ACE (I/D) in Polish Male Half Marathoners. J. Hum. Kinet. 2018, 64, 87–98. [CrossRef]
233. Hudson, D.E.; Mokone, G.G.; Noakes, T.D.; Collins, M. The -55 C/T polymorphism within the UCP3 gene and performance
during the South African Ironman Triathlon. Int. J. Sport. Med. 2004, 25, 427–432. [CrossRef]
234. Prior, S.J.; Hagberg, J.M.; Paton, C.M.; Douglass, L.W.; Brown, M.D.; McLenithan, J.C.; Roth, S.M. DNA sequence variation in the
promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption. Am. J. Physiol. Heart Circ.
Physiol. 2006, 290, H1848–H1855. [CrossRef]
235. Ahmetov, I.I.; Khakimullina, A.M.; Popov, D.V.; Missina, S.S.; Vinogradova, O.L.; Rogozkin, V.A. Polymorphism of the vascular
endothelial growth factor gene (VEGF) and aerobic performance in athletes. Hum. Physiol. 2008, 34, 477–481. [CrossRef]
236. Ahmetov, I.I.; Hakimullina, A.M.; Popov, D.V.; Lyubaeva, E.V.; Missina, S.S.; Vinogradova, O.L.; Williams, A.G.; Rogozkin, V.A.
Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes. Eur. J. Appl. Physiol. 2009, 107,
95–103. [CrossRef]
237. Eider, J.; Leonska-Duniec, A.; Maciejewska-Karlowska, A.; Sawczuk, M.; Ficek, K.; Sawczyn, S. The VEGFR2 gene His472Gln
polymorphism in Polish endurance athletes. Int. SportMed. J. 2013, 14, 29–35.
238. Kumagai, K.; Abe, T.; Brechue, W.F.; Ryushi, T.; Takano, S.; Mizuno, M. Sprint performance is related to muscle fascicle length in
male 100-m sprinters. J. Appl. Physiol. 2000, 88, 811–816. [CrossRef]
239. Weyand, P.G.; Davis, J.A. Running performance has a structural basis. J. Exp. Biol. 2005, 208, 2625–2631. [CrossRef]
240. Uth, N. Anthropometric comparison of world-class sprinters and normal populations. J. Sport. Sci. Med. 2005, 4, 608–616.
241. Tønnessen, E.; Haugen, T.; Shalfawi, S.A. Reaction time aspects of elite sprinters in athletic world championships. J. Strength Cond.
Res. 2013, 27, 885–892. [CrossRef]
242. Haugen, T.; Seiler, S.; Sandbakk, Ø.; Tønnessen, E. The Training and Development of Elite Sprint Performance: An Integration of
Scientific and Best Practice Literature. Sport. Med. Open 2019, 5, 44. [CrossRef]
243. Suga, T.; Terada, M.; Tanaka, T.; Miyake, Y.; Ueno, H.; Otsuka, M.; Nagano, A.; Isaka, T. Calcaneus height is a key morphological
factor of sprint performance in sprinters. Sci. Rep. 2020, 10, 15425. [CrossRef]
244. Hall, E.C.R.; Lysenko, E.A.; Semenova, E.A.; Borisov, O.V.; Andryushchenko, O.N.; Andryushchenko, L.B.; Vepkhvadze, T.F.;
Lednev, E.M.; Zmijewski, P.; Popov, D.V.; et al. Prediction of muscle fiber composition using multiple repetition testing. Biol.
Sport 2021, 38, 277–283. [CrossRef]
245. Hughes, D.C.; Day, S.H.; Ahmetov, I.I.; Williams, A.G. Genetics of muscle strength and power: Polygenic profile similarity limits
skeletal muscle performance. J. Sport. Sci. 2011, 29, 1425–1434. [CrossRef]
246. Zempo, H.; Miyamoto-Mikami, E.; Kikuchi, N.; Fuku, N.; Miyachi, M.; Murakami, H. Heritability estimates of muscle strength-
related phenotypes: A systematic review and meta-analysis. Scand. J. Med. Sci. Sport. 2017, 27, 1537–1546. [CrossRef]
247. Woods, D.; Hickman, M.; Jamshidi, Y.; Brull, D.; Vassiliou, V.; Jones, A.; Humphries, S.; Montgomery, H. Elite swimmers and the
D allele of the ACE I/D polymorphism. Hum. Genet. 2001, 108, 230–232. [CrossRef]
248. Costa, A.M.; Silva, A.J.; Garrido, N.D.; Louro, H.; de Oliveira, R.J.; Breitenfeld, L. Association between ACE D allele and elite
short distance swimming. Eur. J. Appl. Physiol. 2009, 106, 785–790. [CrossRef]
249. Boraita, A.; de la Rosa, A.; Heras, M.E.; de la Torre, A.I.; Canda, A.; Rabadán, M.; Díaz, A.E.; González, C.; López, M.; Hernández,
M. Cardiovascular adaptation, functional capacity and Angiotensin-converting enzyme I/D polymorphism in elite athletes. Rev.
Esp. Cardiol. 2010, 63, 810–819. [CrossRef] [PubMed]
250. Papadimitriou, I.D.; Lucia, A.; Pitsiladis, Y.P.; Pushkarev, V.P.; Dyatlov, D.A.; Orekhov, E.F.; Artioli, G.G.; Guilherme, J.P.; Lancha,
A.H., Jr.; Ginevičienė, V.; et al. ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: A multi-cohort
study. BMC Genom. 2016, 17, 285. [CrossRef] [PubMed]
251. Amir, O.; Amir, R.; Yamin, C.; Attias, E.; Eynon, N.; Sagiv, M.; Sagiv, M.; Meckel, Y. The ACE deletion allele is associated with
Israeli elite endurance athletes. Exp. Physiol. 2007, 92, 881–886. [CrossRef] [PubMed]
252. Kim, C.H.; Cho, J.Y.; Jeon, J.Y.; Koh, Y.G.; Kim, Y.M.; Kim, H.J.; Park, M.; Um, H.S.; Kim, C. ACE DD genotype is unfavorable to
Korean short-term muscle power athletes. Int. J. Sport. Med. 2010, 31, 65–71. [CrossRef] [PubMed]
253. Shahmoradi, S.; Ahmadalipour, A.; Salehi, M. Evaluation of ACE gene I/D polymorphism in Iranian elite athletes. Adv. Biomed.
Res. 2014, 3, 207. [CrossRef]
Genes 2023, 14, 1235 29 of 32

254. Scott, R.A.; Irving, R.; Irwin, L.; Morrison, E.; Charlton, V.; Austin, K.; Tladi, D.; Deason, M.; Headley, S.A.; Kolkhorst, F.W.; et al.
ACTN3 and ACE genotypes in elite Jamaican and US sprinters. Med. Sci. Sport. Exerc. 2010, 42, 107–112. [CrossRef]
255. Windelinckx, A.; De Mars, G.; Huygens, W.; Peeters, M.W.; Vincent, B.; Wijmenga, C.; Lambrechts, D.; Delecluse, C.; Roth, S.M.;
Metter, E.J.; et al. Comprehensive fine mapping of chr12q12-14 and follow-up replication identify activin receptor 1B (ACVR1B)
as a muscle strength gene. Eur. J. Hum. Genet. 2011, 19, 208–215. [CrossRef]
256. Voisin, S.; Guilherme, J.P.; Yan, X.; Pushkarev, V.P.; Cieszczyk, P.; Massidda, M.; Calò, C.M.; Dyatlov, D.A.; Kolupaev, V.A.;
Pushkareva, Y.E.; et al. ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but
Not Brazilians. PLoS ONE 2016, 11, e0156316. [CrossRef]
257. Venckunas, T.; Degens, H. Genetic polymorphisms of muscular fitness in young healthy men. PLoS ONE 2022, 17, e0275179.
[CrossRef]
258. Druzhevskaya, A.M.; Ahmetov, I.I.; Astratenkova, I.V.; Rogozkin, V.A. Association of the ACTN3 R577X polymorphism with
power athlete status in Russians. Eur. J. Appl. Physiol. 2008, 103, 631–634. [CrossRef]
259. Massidda, M.; Vona, G.; Calò, C.M. Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in
Italy. Genet. Test. Mol. Biomark. 2009, 13, 377–380. [CrossRef]
260. Chiu, L.L.; Wu, Y.F.; Tang, M.T.; Yu, H.C.; Hsieh, L.L.; Hsieh, S.S. ACTN3 genotype and swimming performance in Taiwan. Int. J.
Sport. Med. 2011, 32, 476–480. [CrossRef]
261. Ahmetov, I.I.; Druzhevskaya, A.M.; Lyubaeva, E.V.; Popov, D.V.; Vinogradova, O.L.; Williams, A.G. The dependence of preferred
competitive racing distance on muscle fibre type composition and ACTN3 genotype in speed skaters. Exp. Physiol. 2011, 96,
1302–1310. [CrossRef]
262. Ci˛eszczyk, P.; Eider, J.; Ostanek, M.; Arczewska, A.; Leońska-Duniec, A.; Sawczyn, S.; Ficek, K.; Krupecki, K. Association of the
ACTN3 R577X Polymorphism in Polish Power-Orientated Athletes. J. Hum. Kinet. 2011, 28, 55–61. [CrossRef]
263. Yang, R.; Shen, X.; Wang, Y.; Voisin, S.; Cai, G.; Fu, Y.; Xu, W.; Eynon, N.; Bishop, D.J.; Yan, X. ACTN3 R577X Gene Variant Is
Associated With Muscle-Related Phenotypes in Elite Chinese Sprint/Power Athletes. J. Strength Cond. Res. 2017, 31, 1107–1115.
[CrossRef]
264. Akazawa, N.; Ohiwa, N.; Shimizu, K.; Suzuki, N.; Kumagai, H.; Fuku, N.; Suzuki, Y. The association of ACTN3 R577X
polymorphism with sports specificity in Japanese elite athletes. Biol. Sport 2022, 39, 905–911. [CrossRef]
265. Koku, F.E.; Karamızrak, S.O.; Çiftçi, A.S.; Taşlıdere, H.; Durmaz, B.; Çoğulu, Ö. The relationship between ACTN3 R577X gene
polymorphism and physical performance in amateur soccer players and sedentary individuals. Biol. Sport 2019, 36, 9–16.
[CrossRef]
266. Zaccagni, L.; Lunghi, B.; Barbieri, D.; Rinaldo, N.; Missoni, S.; Šaric, T.; Šarac, J.; Babic, V.; Rakovac, M.; Bernardi, F.; et al.
Performance prediction models based on anthropometric, genetic and psychological traits of Croatian sprinters. Biol. Sport 2019,
36, 17–23. [CrossRef]
267. Gomez-Gallego, F.; Santiago, C.; González-Freire, M.; Yvert, T.; Muniesa, C.A.; Serratosa, L.; Altmäe, S.; Ruiz, J.R.; Lucia, A. The C
allele of the AGT Met235Thr polymorphism is associated with power sports performance. Appl. Physiol. Nutr. Metab. 2009, 34,
1108–1111. [CrossRef]
268. Zar˛ebska, A.; Sawczyn, S.; Kaczmarczyk, M.; Ficek, K.; Maciejewska-Karłowska, A.; Sawczuk, M.; Leońska-Duniec, A.; Eider, J.;
Grenda, A.; Ci˛eszczyk, P. Association of rs699 (M235T) polymorphism in the AGT gene with power but not endurance athlete
status. J. Strength Cond. Res. 2013, 27, 2898–2903. [CrossRef]
269. Cieszczyk, P.; Ostanek, M.; Leońska-Duniec, A.; Sawczuk, M.; Maciejewska, A.; Eider, J.; Ficek, K.; Sygit, K.; Kotarska, K.
Distribution of the AMPD1 C34T polymorphism in Polish power-oriented athletes. J. Sport. Sci. 2012, 30, 31–35. [CrossRef]
[PubMed]
270. Fedotovskaya, O.N.; Danilova, A.A.; Akhmetov, I.I. Effect of AMPD1 gene polymorphism on muscle activity in humans. Bull.
Exp. Biol. Med. 2013, 154, 489–491. [CrossRef] [PubMed]
271. Guilherme, J.P.L.F.; Semenova, E.A.; Borisov, O.V.; Kostryukova, E.S.; Vepkhvadze, T.F.; Lysenko, E.A.; Andryushchenko, O.N.;
Andryushchenko, L.B.; Lednev, E.M.; Larin, A.K.; et al. The BDNF-Increasing Allele is Associated with Increased Proportion of
Fast-Twitch Muscle Fibers, Handgrip Strength, and Power Athlete Status. J. Strength Cond. Res. 2022, 36, 1884–1889. [CrossRef]
[PubMed]
272. Fedotovskaya, O.; Eider, J.; Ci˛eszczyk, P.; Ahmetov, I.; Moska, W.; Sawczyn, S.; Leońska–Duniec, A.; Maciejewska-Karłowska, A.;
Sawczuk, M.; Czubek, Z.; et al. Association of muscle-specific creatine kinase (CKM) gene polymorphism with combat athlete
status in Polish and Russian cohorts. Arch. Budo. 2013, 9, 233–237.
273. He, E.P.; Li, Y.H.; Qian, J.D.; Yan, H.W. Association of CKMM gene A/G polymorphism and athletic performance of uyghurna-
tionality. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2016, 32, 82–86.
274. Ginevičienė, V.; Jakaitienė, A.; Utkus, A.; Hall, E.C.R.; Semenova, E.A.; Andryushchenko, L.B.; Larin, A.K.; Moreland, E.;
Generozov, E.V.; Ahmetov, I.I. CKM Gene rs8111989 Polymorphism and Power Athlete Status. Genes 2021, 12, 1499. [CrossRef]
275. Miyamoto-Mikami, E.; Fujita, Y.; Murakami, H.; Ito, M.; Miyachi, M.; Kawahara, T.; Fuku, N. CNTFR Genotype and Sprint/power
Performance: Case-control Association and Functional Studies. Int. J. Sport. Med. 2016, 37, 411–417. [CrossRef]
276. Zmijewski, P.; Trybek, G.; Czarny, W.; Leońska-Duniec, A. GALNTL6 Rs558129: A Novel Polymorphism for Swimming
Performance? J. Hum. Kinet. 2021, 80, 199–205. [CrossRef]
Genes 2023, 14, 1235 30 of 32

277. Cieszczyk, P.; Eider, J.; Arczewska, A.; Ostanek, M.; Leońska-Duniec, A.; Sawczyn, S.; Ficek, K.; Jascaniene, N.; Kotarska, K.; Sygit,
K. The HIF1A gene Pro582Ser polymorphism in polish power-orientated athletes. Biol. Sport 2011, 28, 111–114. [CrossRef]
278. Gabbasov, R.T.; Arkhipova, A.A.; Borisova, A.V.; Hakimullina, A.M.; Kuznetsova, A.V.; Williams, A.G.; Day, S.H.; Ahmetov, I.I.
The HIF1A Gene Pro582Ser Polymorphism in Russian Strength Athletes. J. Strength Cond. Res. 2013, 27, 2055–2058. [CrossRef]
279. Drozdovska, S.B.; Dosenko, V.E.; Ahmetov, I.I.; Ilyin, V.N. The association of gene polymorphisms with athlete status in ukrainians.
Biol. Sport 2013, 30, 163–167. [CrossRef]
280. Ben-Zaken, S.; Meckel, Y.; Nemet, D.; Eliakim, A. Can IGF-I polymorphism affect power and endurance athletic performance?
Growth Horm. IGF Res. 2013, 23, 175–178. [CrossRef]
281. Ben-Zaken, S.; Meckel, Y.; Remmel, L.; Nemet, D.; Jürimäe, J.; Eliakim, A. The prevalence of IGF-I axis genetic polymorphisms
among decathlon athletes. Growth Horm. IGF Res. 2022, 64, 101468. [CrossRef]
282. Itaka, T.; Agemizu, K.; Aruga, S.; Machida, S. G Allele of the IGF2 ApaI Polymorphism Is Associated with Judo Status. J. Strength
Cond. Res. 2016, 30, 2043–2048. [CrossRef]
283. Ruiz, J.R.; Buxens, A.; Artieda, M.; Arteta, D.; Santiago, C.; Rodríguez-Romo, G.; Lao, J.I.; Gómez-Gallego, F.; Lucia, A. The -174
G/C polymorphism of the IL6 gene is associated with elite power performance. J. Sci. Med. Sport 2010, 13, 549–553. [CrossRef]
284. Eider, J.; Cieszczyk, P.; Leońska-Duniec, A.; Maciejewska, A.; Sawczuk, M.; Ficek, K.; Kotarska, K. Association of the 174 G/C
polymorphism of the IL6 gene in Polish power-orientated athletes. J. Sport. Med. Phys. Fitness 2013, 53, 88–92.
285. Terruzzi, I.; Senesi, P.; Montesano, A.; La Torre, A.; Alberti, G.; Benedini, S.; Caumo, A.; Fermo, I.; Luzi, L. Genetic polymorphisms
of the enzymes involved in DNA methylation and synthesis in elite athletes. Physiol. Genom. 2011, 43, 965–973. [CrossRef]
286. Zarebska, A.; Ahmetov, I.; Sawczyn, S.; Weiner, A.S.; Kaczmarczyk, M.; Ficek, K.; Maciejewska-Karlowska, A.; Sawczuk, M.;
Leonska-Duniec, A.; Klocek, T.; et al. Association of the MTHFR 1298A>C (rs1801131) polymorphism with speed and strength
sports in Russian and Polish athletes. J. Sport. Sci. 2013, 32, 375–382. [CrossRef]
287. Murtagh, C.F.; Brownlee, T.E.; Rienzi, E.; Roquero, S.; Moreno, S.; Huertas, G.; Lugioratto, G.; Baumert, P.; Turner, D.C.; Lee, D.;
et al. The genetic profile of elite youth soccer players and its association with power and speed depends on maturity status. PLoS
ONE 2020, 15, e0234458. [CrossRef]
288. Nakamichi, R.; Ma, S.; Nonoyama, T.; Chiba, T.; Kurimoto, R.; Ohzono, H.; Olmer, M.; Shukunami, C.; Fuku, N.; Wang, G.; et al.
The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance. Sci. Transl. Med. 2022, 14,
eabj5557. [CrossRef]
289. Maciejewska-Skrendo, A.; Mieszkowski, J.; Kochanowicz, A.; Niespodziński, B.; Cieszczyk, P.; Leźnicka, K.; Leońska-Duniec, A.;
Kolbowicz, M.; Kaczmarczyk, M.; Piskorska, E.; et al. Does the PPARA Intron 7 Gene Variant (rs4253778) Influence Performance
in Power/Strength-Oriented Athletes? A Case-Control Replication Study in Three Cohorts of European Gymnasts. J. Hum. Kinet.
2021, 79, 77–85. [CrossRef] [PubMed]
290. Ahmetov, I.I.; Mozhayskaya, I.A.; Lyubaeva, E.V.; Vinogradova, O.L.; Rogozkin, V.A. PPARG Gene polymorphism and locomotor
activity in humans. Bull. Exp. Biol. Med. 2008, 146, 630–632. [CrossRef] [PubMed]
291. Maciejewska-Karlowska, A.; Sawczuk, M.; Cieszczyk, P.; Zarebska, A.; Sawczyn, S. Association between the Pro12Ala polymor-
phism of the peroxisome proliferator-activated receptor γ gene and strength athlete status. PLoS ONE 2013, 8, e67172. [CrossRef]
[PubMed]
292. Guilherme, J.P.L.F.; Bertuzzi, R.; Lima-Silva, A.E.; Pereira, A.D.C.; Lancha Junior, A.H. Analysis of sports-relevant polymorphisms
in a large Brazilian cohort of top-level athletes. Ann. Hum. Genet. 2018, 82, 254–264. [CrossRef]
293. Ahmetov, I.I.; Naumov, V.A.; Donnikov, A.E.; Maciejewska-Karłowska, A.; Kostryukova, E.S.; Larin, A.K.; Maykova, E.V.; Alexeev,
D.G.; Fedotovskaya, O.N.; Generozov, E.V.; et al. SOD2 gene polymorphism and muscle damage markers in elite athletes. Free
Radic. Res. 2014, 48, 948–955. [CrossRef]
294. Miyamoto-Mikami, E.; Murakami, H.; Tsuchie, H.; Takahashi, H.; Ohiwa, N.; Miyachi, M.; Kawahara, T.; Fuku, N. Lack of
association between genotype score and sprint/power performance in the Japanese population. J. Sci. Med. Sport 2017, 20, 98–103.
[CrossRef]
295. Khanal, P.; He, L.; Herbert, A.J.; Stebbings, G.K.; Onambele-Pearson, G.L.; Degens, H.; Morse, C.I.; Thomis, M.; Williams, A.G.
The Association of Multiple Gene Variants with Ageing Skeletal Muscle Phenotypes in Elderly Women. Genes 2020, 11, 1459.
[CrossRef]
296. Seaborne, R.A.; Hughes, D.C.; Turner, D.C.; Owens, D.J.; Baehr, L.M.; Gorski, P.; Semenova, E.A.; Borisov, O.V.; Larin, A.K.; Popov,
D.V.; et al. UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy. J. Physiol.
2019, 597, 3727–3749. [CrossRef]
297. Kuschel, L.B.; Sonnenburg, D.; Engel, T. Factors of Muscle Quality and Determinants of Muscle Strength: A Systematic Literature
Review. Healthcare 2022, 10, 1937. [CrossRef]
298. Kikuchi, N.; Moreland, E.; Homma, H.; Semenova, E.A.; Saito, M.; Larin, A.K.; Kobatake, N.; Yusupov, R.A.; Okamoto, T.;
Nakazato, K.; et al. Genes and Weightlifting Performance. Genes 2022, 13, 25. [CrossRef]
299. Colakoglu, M.; Cam, F.S.; Kayitken, B.; Cetinoz, F.; Colakoglu, S.; Turkmen, M.; Sayin, M. ACE genotype may have an effect on
single versus multiple set preferences in strength training. Eur. J. Appl. Physiol. 2005, 95, 20–26. [CrossRef]
300. Giaccaglia, V.; Nicklas, B.; Kritchevsky, S.; Mychalecky, J.; Messier, S.; Bleecker, E.; Pahor, M. Interaction between angiotensin
converting enzyme insertion/deletion genotype and exercise training on knee extensor strength in older individuals. Int. J. Sport.
Med. 2008, 29, 40–44. [CrossRef]
Genes 2023, 14, 1235 31 of 32

301. Costa, A.M.; Silva, A.J.; Garrido, N.; Louro, H.; Marinho, D.A.; Cardoso Marques, M.; Breitenfeld, L. Angiotensin-converting
enzyme genotype affects skeletal muscle strength in elite athletes. J. Sport. Sci. Med. 2009, 8, 410–418.
302. Pimjan, L.; Ongvarrasopone, C.; Chantratita, W.; Polpramool, C.; Cherdrungsi, P.; Bangrak, P.; Yimlamai, T. A Study on ACE,
ACTN3, and VDR Genes Polymorphism in Thai Weightlifters. Walailak J. Sci. Technol. (WJST) 2017, 15, 609–626. [CrossRef]
303. Melián Ortiz, A.; Laguarta-Val, S.; Varillas-Delgado, D. Muscle Work and Its Relationship with ACE and ACTN3 Polymorphisms
Are Associated with the Improvement of Explosive Strength. Genes 2021, 12, 1177. [CrossRef]
304. Khanal, P.; Morse, C.I.; He, L.; Herbert, A.J.; Onambélé-Pearson, G.L.; Degens, H.; Thomis, M.; Williams, A.G.; Stebbings, G.K.
Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women. Genes 2022, 13, 982.
[CrossRef]
305. Gineviciene, V.; Jakaitiene, A.; Aksenov, M.O.; Aksenova, A.V.; Astratenkova, A.D.; Egorova, E.S.; Gabdrakhmanova, L.J.; Tubelis,
L.; Kucinskas, V.; Utkus, A. Association analysis of ACE, ACTN3 and PPARGC1A gene polymorphisms in two cohorts of
European strength and power athletes. Biol. Sport 2016, 33, 199. [CrossRef]
306. Roth, S.M.; Walsh, S.; Liu, D.; Metter, E.J.; Ferrucci, L.; Hurley, B.F. The ACTN3 R577X nonsense allele is under-represented in
elite-level strength athletes. Eur. J. Hum. Genet. 2007, 16, 391–394. [CrossRef]
307. Erskine, R.M.; Williams, A.G.; Jones, D.A.; Stewart, C.E.; Degens, H. The individual and combined influence of ACE and ACTN3
genotypes on muscle phenotypes before and after strength training. Scand. J. Med. Sci Sport. 2014, 24, 642–648. [CrossRef]
308. Homma, H.; Saito, M.; Saito, A.; Kozuma, A.; Matsumoto, R.; Matsumoto, S.; Kobatake, N.; Okamoto, T.; Nakazato, K.; Nishiyama,
T.; et al. The Association between Total Genotype Score and Athletic Performance in Weightlifters. Genes 2022, 13, 2091. [CrossRef]
309. Orysiak, J.; Mazur-Różycka, J.; Busko, K.; Gajewski, J.; Szczepanska, B.; Malczewska-Lenczowska, J. Individual and Combined
Influence of ACE and ACTN3 Genes on Muscle Phenotypes in Polish Athletes. J. Strength Cond. Res. 2018, 32, 2776–2782.
[CrossRef] [PubMed]
310. Ben-Zaken, S.; Eliakim, A.; Nemet, D.; Meckel, Y. Genetic Variability among Power Athletes: The Stronger vs. Faster. J. Strength
Cond. Res. 2019, 33, 1505–1511. [CrossRef] [PubMed]
311. Aleksandra, Z.; Zbigniew, J.; Waldemar, M.; Agata, L.D.; Mariusz, K.; Marek, S.; Agnieszka, M.S.; Piotr, Ż.; Krzysztof, F.; Grzegorz,
T.; et al. The AGT Gene M235T Polymorphism and Response of Power-Related Variables to Aerobic Training. J. Sport. Sci. Med.
2016, 15, 616–624. [PubMed]
312. Matteini, A.M.; Tanaka, T.; Karasik, D.; Atzmon, G.; Chou, W.C.; Eicher, J.D.; Johnson, A.D.; Arnold, A.M.; Callisaya, M.L.; Davies,
G.; et al. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell 2016, 15,
792–800. [CrossRef] [PubMed]
313. Walsh, S.; Zmuda, J.M.; Cauley, J.A.; Shea, P.R.; Metter, E.J.; Hurley, B.F.; Ferrell, R.E.; Roth, S.M. Androgen receptor CAG repeat
polymorphism is associated with fat-free mass in men. J. Appl. Physiol. 2005, 98, 132–137. [CrossRef]
314. Guilherme, J.P.L.; Shikhova, Y.V.; Dondukovskaya, R.R.; Topanova, A.A.; Semenova, E.A.; Astratenkova, I.V.; Ahmetov, I.I.
Androgen receptor gene microsatellite polymorphism is associated with muscle mass and strength in bodybuilders and power
athlete status. Ann. Hum. Biol. 2021, 48, 142–149. [CrossRef]
315. Fedotovskaia, O.N.; Popov, D.V.; Vinogradova, O.L.; Akhmetov, I.I. Association of the muscle-specific creatine kinase (CKMM)
gene polymorphism with physical performance of athletes. Fiziol. Cheloveka 2012, 38, 105–109. [CrossRef]
316. Homma, H.; Kobatake, N.; Sekimoto, Y.; Saito, M.; Mochizuki, Y.; Okamoto, T.; Nakazato, K.; Nishiyama, T.; Kikuchi, N. Ciliary
Neurotrophic Factor Receptor rs41274853 Polymorphism Is Associated with Weightlifting Performance in Japanese Weightlifters.
J. Strength Cond. Res. 2020, 34, 3037–3041. [CrossRef]
317. Grishina, E.E.; Zmijewski, P.; Semenova, E.A.; Ci˛eszczyk, P.; Humińska-Lisowska, K.; Michałowska-Sawczyn, M.; Maculewicz, E.;
Crewther, B.; Orysiak, J.; Kostryukova, E.S.; et al. Three DNA Polymorphisms Previously Identified as Markers for Handgrip
Strength Are Associated with Strength in Weightlifters and Muscle Fiber Hypertrophy. J. Strength Cond. Res. 2019, 33, 2602–2607.
[CrossRef]
318. Ahmetov, I.I.; Hakimullina, A.M.; Lyubaeva, E.V.; Vinogradova, O.L.; Rogozkin, V.A. Effect of HIF1A gene polymorphism on
human muscle performance. Bull. Exp. Biol. Med. 2008, 146, 351–353. [CrossRef]
319. Kostek, M.C.; Devaney, J.M.; Gordish-Dressman, H.; Harris, T.B.; Thompson, P.D.; Clarkson, P.M.; Angelopoulos, T.J.; Gordon,
P.M.; Moyna, N.M.; Pescatello, L.S.; et al. A polymorphism near IGF1 is associated with body composition and muscle function in
women from the Health, Aging, and Body Composition Study. Eur. J. Appl. Physiol. 2010, 110, 315–324. [CrossRef]
320. Ahmetov, I.I.; Gavrilov, D.N.; Astratenkova, I.V.; Druzhevskaya, A.M.; Malinin, A.V.; Romanova, E.E.; Rogozkin, V.A. The
association of ACE, ACTN3 and PPARA gene variants with strength phenotypes in middle school-age children. J. Physiol. Sci.
2013, 63, 79–85. [CrossRef]
321. Petr, M.; Stastny, P.; Pecha, O.; Šteffl, M.; Šeda, O.; Kohlíková, E. PPARA intron polymorphism associated with power performance
in 30-s anaerobic Wingate Test. PLoS ONE 2014, 9, e107171. [CrossRef]
322. Mann, D.L.; Dehghansai, N.; Baker, J. Searching for the elusive gift: Advances in talent identification in sport. Curr. Opin. Psychol.
2017, 16, 128–133. [CrossRef]
323. Johnston, K.; Wattie, N.; Schorer, J.; Baker, J. Talent Identification in Sport: A Systematic Review. Sport. Med. 2018, 48, 97–109.
[CrossRef]
324. Baker, J.; Wilson, S.; Johnston, K.; Dehghansai, N.; Koenigsberg, A.; de Vegt, S.; Wattie, N. Talent Research in Sport 1990-2018: A
Scoping Review. Front. Psychol. 2020, 11, 607710. [CrossRef]
Genes 2023, 14, 1235 32 of 32

325. Wang, G.; Padmanabhan, S.; Wolfarth, B.; Fuku, N.; Lucia, A.; Ahmetov, I.I.; Cieszczyk, P.; Collins, M.; Eynon, N.; Klissouras,
V.; et al. Genomics of elite sporting performance: What little we know and necessary advances. Adv. Genet. 2013, 84, 123–149.
[CrossRef]
326. Webborn, N.; Williams, A.; McNamee, M.; Bouchard, C.; Pitsiladis, Y.; Ahmetov, I.; Ashley, E.; Byrne, N.; Camporesi, S.; Collins,
M.; et al. Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement. Br.
J. Sport. Med 2015, 49, 1486–1491. [CrossRef]
327. Pitsiladis, Y.P.; Tanaka, M.; Eynon, N.; Bouchard, C.; North, K.N.; Williams, A.G.; Collins, M.; Moran, C.N.; Britton, S.L.; Fuku,
N.; et al. Athlome Project Consortium: A concerted effort to discover genomic and other “omic” markers of athletic performance.
Physiol. Genom. 2016, 48, 183–190. [CrossRef]
328. de la Chapelle, A.; Sistonen, P.; Lehväslaiho, H.; Ikkala, E.; Juvonen, E. Familial erythrocytosis genetically linked to erythropoietin
receptor gene. Lancet 1993, 341, 82–84. [CrossRef]
329. Schuelke, M.; Wagner, K.R.; Stolz, L.E.; Hübner, C.; Riebel, T.; Kömen, W.; Braun, T.; Tobin, J.F.; Lee, S.J. Myostatin mutation
associated with gross muscle hypertrophy in a child. N. Engl. J. Med. 2004, 350, 2682–2688. [CrossRef] [PubMed]
330. Turner, D.C.; Gorski, P.P.; Maasar, M.F.; Seaborne, R.A.; Baumert, P.; Brown, A.D.; Kitchen, M.O.; Erskine, R.M.; Dos-Remedios, I.;
Voisin, S.; et al. DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: The role of
HOX genes and physical activity. Sci. Rep. 2020, 10, 15360. [CrossRef] [PubMed]
331. Seaborne, R.A.; Strauss, J.; Cocks, M.; Shepherd, S.; O’Brien, T.D.; van Someren, K.A.; Bell, P.G.; Murgatroyd, C.; Morton, J.P.;
Stewart, C.E.; et al. Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy. Sci. Rep. 2018, 8, 1898. [CrossRef]
[PubMed]
332. Turner, D.C.; Seaborne, R.A.; Sharples, A.P. Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle
Anabolism, Hypertrophy and Epigenetic Memory. Sci. Rep. 2019, 9, 4251. [CrossRef]
333. Demirci, B.; Bulgay, C.; Ceylan, H.İ.; Öztürk, M.E.; Öztürk, D.; Kazan, H.H.; Ergun, M.A.; Cerit, M.; Semenova, E.A.; Larin, A.K.; et al.
Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses. Genes 2023, 14, 1190. [CrossRef]
334. Murtagh, C.F.; Hall, E.C.; Brownlee, T.E.; Drust, B.; Williams, A.G.; Erskine, R.M. The genetic association with athlete status,
physical performance and injury risk in soccer. Int. J. Sport. Med. 2023, in press. [CrossRef]

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