Table S1. The characteristics of 268 CT genes identified in our previous study.

ENname CHR Start End Strand Gene Known

ENSG00000007350 chrX 153524024 153558700 + TKTL1 NO
ENSG00000046774 chrX 141290131 141293076 - MAGEC2 YES
ENSG00000068985 chrX 49452053 49460596 - PAGE1 YES
ENSG00000070886 chr1 22890057 22930087 + EPHA8 NO
ENSG00000075886 chr2 132233666 132240507 + TUBA3D NO
ENSG00000080572 chrX 106449862 106487473 + PIH1D3 NO
ENSG00000095627 chr10 115939029 115992063 + TDRD1 YES
ENSG00000099399 chrX 30233677 30238206 + MAGEB2 YES
ENSG00000101448 chr20 44165625 44176391 - EPPIN YES
ENSG00000101890 chrX 108616135 108725301 - GUCY2F NO
ENSG00000102387 chrX 100523241 100548059 - TAF7L YES
ENSG00000103546 chr16 55689516 55740104 + SLC6A2 NO
ENSG00000104755 chr8 39601254 39695808 - ADAM2 YES
ENSG00000104818 chr19 49535169 49536495 + CGB2 NO
ENSG00000104941 chr19 46298968 46318577 - RSPH6A NO
ENSG00000106410 chr7 144094333 144107320 - NOBOX NO
ENSG00000109832 chr11 125773271 125793158 + DDX25 NO
ENSG00000112038 chr6 154331631 154568001 + OPRM1 NO
ENSG00000112238 chr6 100054606 100063454 + PRDM13 NO
ENSG00000112273 chr6 22569678 22571892 + HDGFL1 NO
ENSG00000114349 chr3 50229045 50233949 + GNAT1 NO
ENSG00000114487 chr3 108677086 108836989 - MORC1 YES
ENSG00000116726 chr1 12834984 12838049 + PRAMEF12 NO
ENSG00000117148 chr1 18081808 18153558 + ACTL8 YES
ENSG00000120210 chr9 5131979 5185668 - INSL6 NO
ENSG00000120498 chrX 69748790 70128581 - TEX11 NO
ENSG00000121446 chr1 182419256 182529734 + RGSL1 NO
ENSG00000123569 chrX 103265719 103268259 - H2BFWT NO
ENSG00000123576 chrX 103494719 103499614 - ESX1 NO
ENSG00000123584 chrX 148663309 148669116 - MAGEA9B YES
ENSG00000124092 chr20 56071035 56100708 - CTCFL YES
ENSG00000124260 chrX 151301782 151307033 - MAGEA10 YES
ENSG00000124678 chr6 35085848 35116387 - TCP11 NO
ENSG00000125207 chr12 130822432 130857182 + PIWIL1 YES
ENSG00000125788 chr20 123010 126392 + DEFB126 NO
ENSG00000126752 chrX 48114752 48126879 + SSX1 YES
ENSG00000129221 chr17 6297013 6338519 - AIPL1 NO
ENSG00000131050 chr20 31749574 31769218 + BPIFA2 NO
ENSG00000131126 chr19 43905648 43922763 + TEX101 YES
ENSG00000131738 chr17 39519746 39526052 - KRT33B NO
ENSG00000131914 chr1 26737269 26756213 + LIN28A NO
ENSG00000132446 chrX 31089360 31090170 - FTHL17 YES
ENSG00000133980 chr14 74769772 74826711 + VRTN NO
ENSG00000134588 chrX 132158659 132231137 - USP26 NO
ENSG00000134640 chr11 92702886 92718232 + MTNR1B NO
ENSG00000135248 chr7 128349115 128371797 + FAM71F1 NO
ENSG00000137674 chr11 102447566 102496063 - MMP20 NO
ENSG00000138684 chr4 123533783 123542224 - IL21 NO
ENSG00000138813 chr4 100432161 100463460 + C4orf17 NO
ENSG00000139151 chr12 18836103 18890991 - PLCZ1 NO
ENSG00000139445 chr12 109715784 109747025 - FOXN4 NO
ENSG00000140623 chr16 4827670 4838522 - 43355 NO
ENSG00000140798 chr16 48116884 48189929 - ABCC12 NO
ENSG00000141096 chr16 68009566 68014732 - DPEP3 NO
ENSG00000141255 chr17 3343313 3417146 - SPATA22 NO
ENSG00000141316 chr17 31297394 31324895 + SPACA3 YES
ENSG00000142025 chr19 42348806 42356401 + DMRTC2 NO
ENSG00000142513 chr19 51293672 51298481 + ACPT NO
ENSG00000142698 chr1 34632484 34684732 + C1orf94 NO
ENSG00000143006 chr1 53925072 53933161 + DMRTB1 NO
ENSG00000143032 chr1 91177096 91182794 - BARHL2 NO
ENSG00000143194 chr1 166958346 166991451 + MAEL YES
ENSG00000144015 chr2 96257766 96265526 + TRIM43 NO
ENSG00000145309 chr4 71200683 71202833 + CABS1 NO
ENSG00000146276 chr6 89887220 89940997 - GABRR1 NO
ENSG00000146453 chr6 160221298 160241736 + PNLDC1 NO
ENSG00000147183 chrX 88002226 88009786 + CPXCR1 YES
ENSG00000147381 chrX 151080981 151093642 + MAGEA4 YES
ENSG00000151005 chr4 164392257 164395047 - TKTL2 NO
ENSG00000151033 chr10 30900718 30918691 - LYZL2 NO
ENSG00000151360 chr2 3705785 3750261 + ALLC NO
ENSG00000151615 chr4 147560045 147563626 + POU4F2 NO
ENSG00000151962 chr4 155702365 155749965 + RBM46 YES
ENSG00000152086 chr2 130949318 130956034 - TUBA3E NO
ENSG00000152208 chr4 93225550 94695707 + GRID2 NO
ENSG00000152463 chr10 15074226 15115851 + OLAH NO
ENSG00000152670 chr5 55033845 55112985 + DDX4 NO
ENSG00000153779 chrX 89176881 89177882 + TGIF2LX NO
ENSG00000154143 chr11 124481386 124490252 + PANX3 NO
ENSG00000154438 chr7 117003276 117068177 - ASZ1 NO
ENSG00000154611 chr18 23713816 23773319 + PSMA8 NO
ENSG00000154997 chr7 55861237 55930482 - 43357 NO
ENSG00000155495 chrX 140991680 140997174 + MAGEC1 YES
ENSG00000155875 chr9 18927656 19033251 - FAM154A NO
ENSG00000156009 chrX 149009941 149014609 + MAGEA8 YES
ENSG00000156269 chr4 80146848 80247204 - NAA11 NO
ENSG00000157060 chr1 182869000 182922660 - SHCBP1L NO
ENSG00000157884 chr2 26804070 26864236 - CIB4 NO
ENSG00000158639 chrX 55246788 55250541 + PAGE5 YES
ENSG00000159224 chr17 47035916 47045958 - GIP NO
ENSG00000160505 chr19 56347944 56393220 + NLRP4 YES
ENSG00000161040 chr7 102453308 102715286 - FBXL13 NO
ENSG00000161609 chr19 49891475 49921251 + CCDC155 NO
ENSG00000161652 chr19 50655805 50666452 - IZUMO2 NO
ENSG00000162039 chr16 1883984 1934295 - MEIOB NO
ENSG00000162624 chr1 75594119 75627218 + LHX8 NO
ENSG00000162753 chr1 173469603 173572233 - SLC9C2 NO
ENSG00000162771 chr1 212797789 212800120 + FAM71A NO
ENSG00000163206 chr1 152850793 152857523 + SMCP NO
ENSG00000163263 chr1 154171848 154178809 - C1orf189 NO
ENSG00000163424 chr3 118864997 118878889 + C3orf30 NO
ENSG00000163440 chr4 56422692 56458379 - PDCL2 NO
ENSG00000163530 chr3 109012635 109035364 - DPPA2 YES
ENSG00000163793 chr2 27498289 27504367 + DNAJC5G NO
ENSG00000164256 chr5 23507264 23528706 + PRDM9 NO
ENSG00000164299 chr5 79615444 79617661 + SPZ1 NO
ENSG00000164744 chr7 48026745 48068716 - SUN3 NO
ENSG00000164900 chr7 150845676 150871832 - GBX1 NO
ENSG00000165131 chr7 142636440 142637955 + C7orf34 NO
ENSG00000165496 chr14 47120222 47121028 - RPL10L NO
ENSG00000165583 chrX 48045656 48056199 - SSX5 YES
ENSG00000165584 chrX 48205863 48216142 - SSX3 YES
ENSG00000165643 chr9 138585253 138591374 - SOHLH1 NO
ENSG00000165863 chr10 118423207 118429775 - C10orf82 NO
ENSG00000165972 chr12 96260826 96336752 - CCDC38 NO
ENSG00000166049 chrX 150732094 150845211 + PASD1 YES
ENSG00000166069 chr15 38214140 38259925 + TMCO5A NO
ENSG00000166118 chr11 133710526 133715433 - SPATA19 YES
ENSG00000166800 chr11 18477371 18501147 + LDHAL6A NO
ENSG00000166926 chr11 60102304 60164069 + MS4A6E NO
ENSG00000168070 chr11 64704989 64739557 - C11orf85 NO
ENSG00000168454 chr18 9885763 9889272 + TXNDC2 NO
ENSG00000168757 chrY 6114264 6117060 + TSPY2 YES
ENSG00000168930 chr11 89530823 89541743 - TRIM49 NO
ENSG00000169059 chrX 6451659 6453159 - VCX3A NO
ENSG00000169551 chrX 134290461 134305322 - CXorf48 YES
ENSG00000170279 chr7 148287657 148312952 + C7orf33 NO
ENSG00000170486 chr12 52979373 52995322 - KRT72 NO
ENSG00000170516 chr4 46736844 46911252 - COX7B2 NO
ENSG00000170788 chr10 82095861 82116511 - DYDC1 NO
ENSG00000171102 chr9 136080664 136084630 - OBP2B NO
ENSG00000171209 chr4 71108305 71117145 + CSN3 NO
ENSG00000171405 chrX 52841228 52847325 + XAGE5 YES
ENSG00000171487 chr19 56511092 56573179 + NLRP5 NO
ENSG00000171772 chr10 135367404 135382876 - SYCE1 YES
ENSG00000171804 chr19 38375463 38397317 - WDR87 NO
ENSG00000171956 chr15 60296421 60353929 + FOXB1 NO
ENSG00000172967 chr22 17264302 17302589 - XKR3 NO
ENSG00000173809 chr19 33210659 33320483 + TDRD12 NO
ENSG00000174016 chrX 79591003 79700810 + FAM46D YES
ENSG00000175018 chr10 127265091 127371713 - TEX36 NO
ENSG00000175294 chr11 65784223 65793988 - CATSPER1 NO
ENSG00000175664 chr13 31506840 31549639 + TEX26 NO
ENSG00000176294 chr14 20187174 20296531 + OR4N2 NO
ENSG00000176566 chr8 88882973 88886296 - DCAF4L2 NO
ENSG00000176635 chr22 30476163 30573064 + HORMAD2 YES
ENSG00000176679 chrY 3447082 3448082 + TGIF2LY NO
ENSG00000176746 chrX 26210557 26213763 + MAGEB6 YES
ENSG00000177138 chrX 8992273 9132680 - FAM9B NO
ENSG00000177414 chr1 64669310 64733051 + UBE2U NO
ENSG00000177627 chr12 48876286 48890295 + C12orf54 NO
ENSG00000177689 chrX 27826107 27841131 + MAGEB10 NO
ENSG00000177938 chr12 18891045 18892121 + CAPZA3 NO
ENSG00000177992 chr9 90497741 90503814 + SPATA31E1 NO
ENSG00000177994 chr2 54557171 54610879 + C2orf73 NO
ENSG00000178125 chr8 67876334 67968839 - PPP1R42 NO
ENSG00000178403 chr4 113434672 113437328 - NEUROG2 NO
ENSG00000178645 chr10 50887697 50918307 + C10orf53 NO
ENSG00000179046 chr4 189012427 189030757 - TRIML2 NO
ENSG00000179059 chr4 188916925 188926204 + ZFP42 NO
ENSG00000179709 chr19 56459198 56499995 + NLRP8 NO
ENSG00000179873 chr19 56296770 56348166 - NLRP11 NO
ENSG00000180043 chr19 55866276 55874628 - FAM71E2 NO
ENSG00000180083 chr20 44277202 44298909 - WFDC11 NO
ENSG00000180869 chr1 85093913 85100703 - C1orf180 NO
ENSG00000181433 chrX 134971374 134995220 + SAGE1 YES
ENSG00000181562 chr14 21214051 21216539 + EDDM3A NO
ENSG00000181781 chr19 463346 474983 - ODF3L2 NO
ENSG00000181786 chr19 8807751 8809172 - ACTL9 NO
ENSG00000182111 chr7 57509883 57533252 + ZNF716 NO
ENSG00000182459 chr17 80317123 80321652 + TEX19 NO
ENSG00000182583 chrX 7810303 7812184 + VCX NO
ENSG00000183324 chr15 73735499 73852355 + C15orf60 YES
ENSG00000183434 chrX 132350697 132352376 - TFDP3 YES
ENSG00000183559 chr10 124457225 124459338 - C10orf120 NO
ENSG00000183629 chr15 28764757 28778160 - GOLGA8G NO
ENSG00000183654 chr5 16067248 16180871 - 43170 NO
ENSG00000183706 chr15 22382382 22383507 + OR4N4 NO
ENSG00000184029 chr21 39323728 39493454 - DSCR4 NO
ENSG00000184033 chrX 153845865 153847533 - CTAG1B YES
ENSG00000184478 chr11 5968570 5969591 + OR56A3 NO
ENSG00000184507 chr15 34635516 34649938 + NUTM1 NO
ENSG00000184571 chr22 25115001 25170687 - PIWIL3 NO
ENSG00000184735 chrX 23018087 23020204 + DDX53 YES
ENSG00000185177 chr7 57187321 57207571 - ZNF479 NO
ENSG00000185247 chrX 148769894 148798926 + MAGEA11 YES
ENSG00000185775 chr9 43624507 43630730 - SPATA31A6 NO

ENSG00000185823 chr15 24920541 24928593 + NPAP1 NO

ENSG00000186075 chr17 38024417 38034149 + ZPBP2 NO
ENSG00000186086 chr1 108918421 109013624 + NBPF6 NO
ENSG00000186453 chr2 24397938 24423718 + FAM228A NO
ENSG00000187268 chrX 13053737 13062801 - FAM9C NO
ENSG00000187516 chrX 37850070 37850569 + CXorf27 NO
ENSG00000187533 chr4 70999333 71042516 + C4orf40 NO
ENSG00000187537 chr14 19983559 20020272 - POTEM NO
ENSG00000187581 chr14 93813537 93814702 + COX8C NO
ENSG00000187600 chr2 46656329 46711564 + TMEM247 NO
ENSG00000187690 chrX 51149767 51151687 + CXorf67 NO
ENSG00000187772 chr6 105404923 105531207 + LIN28B NO
ENSG00000187806 chr15 72690614 72700370 + TMEM202 NO
ENSG00000189023 chrX 35816459 35821852 + MAGEB16 NO
ENSG00000189064 chrX 49354132 49361430 + GAGE2A YES
ENSG00000189299 chrX 55649833 55652621 + FOXR2 NO
ENSG00000196119 chr11 124439893 124441037 + OR8A1 NO
ENSG00000196242 chr1 247693434 247697141 - OR2C3 NO
ENSG00000196427 chr1 108765963 108786689 - NBPF4 NO
ENSG00000196431 chr22 27017928 27026636 + CRYBA4 NO
ENSG00000196844 chr11 125646008 125648714 - PATE2 NO
ENSG00000197123 chr7 63688852 63727309 + ZNF679 NO
ENSG00000197181 chr8 22132810 22215076 + PIWIL2 YES
ENSG00000197416 chr8 82437216 82443613 - FABP12 NO
ENSG00000197826 chr4 81256874 81884910 + C4orf22 NO
ENSG00000198028 chr19 9577183 9609283 - ZNF560 NO
ENSG00000198033 chr13 19747910 19755992 - TUBA3C NO
ENSG00000198054 chr21 39493545 39560110 + DSCR8 YES
ENSG00000198062 chr22 16256441 16287937 - POTEH YES
ENSG00000198173 chrX 37026432 37029739 + FAM47C NO
ENSG00000198573 chrX 140335596 140336629 - SPANXC YES
ENSG00000198681 chrX 152481522 152486115 - MAGEA1 YES
ENSG00000198704 chr6 28471073 28495992 - GPX6 NO
ENSG00000198765 chr1 115397424 115537991 + SYCP1 YES
ENSG00000198798 chrX 30248553 30255607 + MAGEB3 YES
ENSG00000198883 chrX 152157368 152162671 - PNMA5 NO
ENSG00000198889 chrX 125683369 125686834 - DCAF12L1 NO
ENSG00000203909 chr6 74062785 74064018 - DPPA5 NO
ENSG00000203926 chrX 140677562 140678899 + SPANXA2 YES
ENSG00000203963 chr1 67557848 67697536 - C1orf141 NO
ENSG00000203989 chrX 119205848 119211707 - RHOXF2B NO
ENSG00000204661 chr5 179068545 179072047 - C5orf60 NO
ENSG00000204671 chr12 122656577 122658746 - IL31 NO
ENSG00000204961 chr5 140227048 140391929 + PCDHA9 NO
ENSG00000205108 chr9 34723052 34729464 - FAM205A NO
ENSG00000205111 chr2 39402787 39456729 - CDKL4 NO
ENSG00000205212 chr17 20739760 20799453 - CCDC144NL NO
ENSG00000205642 chrX 8432871 8434550 + VCX3B NO
ENSG00000205777 chrX 49363628 49373139 + GAGE1 YES
ENSG00000213218 chr17 61949372 61951126 - CSH2 NO
ENSG00000213231 chr14 96152754 96158980 + TCL1B NO
ENSG00000214107 chrX 30261847 30270155 + MAGEB1 YES
ENSG00000214415 chr7 80087987 80141336 - GNAT3 NO
ENSG00000215262 chr8 36641842 36793646 + KCNU1 NO
ENSG00000215343 chr8 11961898 11973025 + ZNF705D NO
ENSG00000215568 chr22 17442826 17489112 - GAB4 NO
ENSG00000221882 chr17 3181193 3182268 - OR3A2 NO
ENSG00000224659 chrX 49178536 49185863 + GAGE12J YES
ENSG00000226372 chrX 27996110 27999566 - DCAF8L1 NO
ENSG00000226941 chrY 24454970 24564028 + RBMY1J NO
ENSG00000227488 chrX 49306370 49313697 + GAGE12D YES
ENSG00000228927 chrY 9236030 9307357 + TSPY3 YES
ENSG00000229937 chr7 18066405 18067486 - PRPS1L1 NO
ENSG00000231171 chr4 178649911 178911904 + RP11-389E17.1 NO
ENSG00000232423 chr1 12998181 13117751 - PRAMEF6 NO
ENSG00000233803 chrY 9175073 9177893 + TSPY4 NO
ENSG00000234068 chrX 55115441 55119275 + PAGE2 YES
ENSG00000234414 chrY 23673258 23711212 + RBMY1A1 NO
ENSG00000236311 chr10 102849078 102890883 - TLX1NB NO
ENSG00000236446 chrX 120006457 120009779 - CT47B1 YES
ENSG00000237136 chr4 146601356 146692184 + C4orf51 NO
ENSG00000238269 chrX 55101496 55105342 + PAGE2B YES
ENSG00000240021 chr1 178482212 178517734 + TEX35 NO
ENSG00000241476 chrX 52725946 52736239 - SSX2 YES
ENSG00000243543 chr20 44162835 44168134 - WFDC6 NO
ENSG00000250423 chrX 118212598 118284542 - KIAA1210 NO
ENSG00000251258 chr6 112668532 112672498 + RFPL4B NO
ENSG00000255181 chr8 144788864 144790279 - CCDC166 NO
ENSG00000258713 chr20 2795633 2796479 + C20orf141 NO
ENSG00000258992 chrY 9236076 9307357 + TSPY1 NO
ENSG00000261509 chr16 33261515 33264716 + TP53TG3B NO
Table S2. Information of primers for Sequenom MassARRAY iPLEX.

Variants Sequence (5'-3')

F: ACGTTGGATGAGGCTCTGGCTTATGGTTGA
rs12645087 R: ACGTTGGATGCTGACCTTCACGTGTTTTAC
E: ccCGTGTTTTACATAATAAAATGCC
F: ACGTTGGATGGCCGCTATAAACTAGAATGG
rs145033304 R: ACGTTGGATGACACTGACTTCCACAATGGC
E: CACTGTTGGTGGGAC
F: ACGTTGGATGATGGTCTTACTGATCAGAGG
rs17135666 R: ACGTTGGATGATCTGCACATCACATCTCCC
E: tggtCAACCCAAATTTTCCCT
F: ACGTTGGATGCTTGGATTTTAGTTGGCAAAG
rs175150 R: ACGTTGGATGAGTTTATTGCGCAAGTGAGG
E: ctcgTCTTCATTACAATTCATACCTAG
F: ACGTTGGATGAGACACAAGTAGGTTAACAG
rs3123484 R: ACGTTGGATGTGTCTCTAGCAACAATTGTG
E: AGAGCTGGGGTGGCTA
F: ACGTTGGATGCTAGACCTAAGAAGCAAGGG
rs402969 R: ACGTTGGATGTGCATTGCACCGATTGGAAG
E: gggatCTCCCTTGATTCAGAATGAATG
F: ACGTTGGATGGGAGACCCACTAAATTGCTG
rs60813831 R: ACGTTGGATGCCTGTCTGGACTAAATCCTG
E: ctacATCCTGTTTTAGTCAGCAG
F: ACGTTGGATGGGAAATATGTGATCAGGAGG
rs6941653 R: ACGTTGGATGGTTGAGCATTTTTTGGCAGG
E: TTCCAATATATTTCTTTAGAAAATGT
F: ACGTTGGATGCTCCCCTCTTTATACACACG
rs7546603 R: ACGTTGGATGTGAGGTCCTGCACATACGG
E: gggagACACACGTATGAAAATACATCTA
F: ACGTTGGATGAGAGGCAGAGGGAAGCATAG
rs77027865 R: ACGTTGGATGGACATGGCAGTGATTTTTGAC
E: atGCTGGAGAAAGGACAG
F: ACGTTGGATGCCTGCTTATATTTCCATTGC
rs79461429 R: ACGTTGGATGACAAGATCGATCTGCATCTG
E: ACCTGTAAAGACACACA
F: ACGTTGGATGAGTGATGCGCTGAGTTCTTC
rs79727953 R: ACGTTGGATGACAAAGGTTATCCTGGGTGG
E：gacgGGGTGGGCCTGACCTAATCAA
F: ACGTTGGATGGAGAAGTCTCTAATCTCCTC
rs8139987 R: ACGTTGGATGACTTGATGTGAATGGATGGG
E: ggCAGTTTTTGGAAACATGC
rs9478496 F: ACGTTGGATGTGGACTTCCACTTCCAAATG
 R: ACGTTGGATGCAGTCCAAACCTTTTGCTGA
E: TTTTAGCAGTTATATGATGAGAC
F: ACGTTGGATGGACAGTAACACAGTGGTTTC
rs6851719 R: ACGTTGGATGGACTGCATTCATCATGTGGC
E: ATTTGCTTTTAATCACTGTTC
F: ACGTTGGATGGGCATACAATCAGACAAGAC
rs75932085
(rs144031443) R: ACGTTGGATGACCAGTCATCAGGAATAAGG
E: GCTGGTTTACTGGGTTA
F: ACGTTGGATGTTCTGGGACATGAGTGCATC
rs4726004
(rs150492976) R: ACGTTGGATGTGGTGACTCCTGAAACTCTG
E: ATGAGTGCATCTTTGGGTA
Note: primers for rs144031443 and rs150492976 were not successfully designed due to
too much “ATATAT” in the sequences. These two variants were replaced by rs75932085
(r2 = 0.66) and rs4726004 (r2 = 1), respectively.
Table S3. Interaction analysis between our identified SNPs (rs6941653 and rs402969) and smoking.

rs6941653 Genotype
Stage Smoke TT TC CC P_interaction
Cases/Controls OR (95%CI) P Cases/Controls OR (95%CI) P Cases/Controls OR (95%CI) P
NO 497/1111 1.00 Reference 286/588 1.10(0.92-1.31) 0.292 42/69 1.34(0.90-2.00) 0.155
NJMU GWAS 0.287
Yes 863/835 3.17(2.67-3.77) 6.58E-39 566/420 4.13(3.41-5.01) 1.51E-47 77/54 4.27(2.93-6.22) 3.81E-14
NO 353/364 1.00 Reference 186/166 1.15(0.89-1.49) 0.272 26/22 1.22(0.68-2.20) 0.501
Validation 0.644
Yes 262/275 1.07(0.83-1.38) 0.597 160/124 1.45(1.07-1.97) 0.016 20/18 1.25(0.64-2.43) 0.513
NO 850/1475 1.00 Reference 472/754 1.09(0.95-1.26) 0.227 68/91 1.29(0.93-1.79) 0.129
Combined 0.172
Yes 1125/1110 2.20(1.91-2.53) 3.41E-28 726/544 2.89(2.47-3.39) 1.80E-39 97/72 2.88(2.08-3.98) 1.69E-10
rs402969 Genotype
Stage Smoke CC CT TT P_interaction
Cases/Controls OR (95%CI) P Cases/Controls OR (95%CI) P Cases/Controls OR (95%CI) P
NO 539/1188 1.00 Reference 249/521 1.07(0.89-1.28) 0.498 37/59 1.33(0.87-2.04) 0.189
NJMU GWAS 0.341
Yes 983/913 3.25(2.75-3.85) 3.89E-43 457/356 3.85(3.16-4.69) 6.61E-41 66/40 5.00(3.29-7.59) 4.47E-14
NO 348/358 1.00 Reference 191/184 1.06(0.83-1.37) 0.628 26/20 1.33(0.73-2.43) 0.355
Validation 0.365
Yes 281/290 1.07(0.83-1.38) 0.614 143/118 1.33(1.00-1.82) 0.049 14/11 1.39(0.62-3.14) 0.423
NO 887/1546 1.00 Reference 440/705 1.09(0.95-1.27) 0.226 63/79 1.36(0.97-1.92) 0.077
Combined 0.222
Yes 1264/1203 2.28(1.99-2.61) 3.54E-32 600/474 2.73(2.32-3.22) 2.07E-33 80/51 3.39(2.35-4.91) 7.94E-11
Table S4. Interaction analysis between risk variant rs6941653 and SNP rs402969.

rs402969 Genotype
rs6941653
Stage CC CT TT P_interaction
Genotype
Cases/Controls OR (95%CI) P Cases/Controls OR (95%CI) P Cases/Controls OR (95%CI) P
TT 894/1357 1.00 Reference 413/532 1.18(1.01-1.38) 0.039 53/57 1.37(0.93-2.04) 0.116
NJMU GWAS TC 548/661 1.25(1.08-1.44) 0.003 262/307 1.32(1.09-1.59) 0.005 42/40 1.64(1.04-2.58) 0.033 0.787
CC 80/83 1.37(0.98-1.90) 0.062 31/38 1.31(0.80-2.16) 0.283 8/2 5.77(1.19-27.94) 0.029
TT 365/424 1.00 Reference 210/191 1.28(1.02-1.63) 0.036 26/18 1.66(0.89-3.08) 0.108
Validation TC 233/178 1.52(1.19-1.93) 6.79E-04 98/93 1.24(0.90-1.70) 0.185 9/11 0.96(0.39-2.34) 0.923 0.094
CC 24/24 1.17(0.65-2.09) 0.904 16/14 1.32(0.63-2.74) 0.461 5/2 2.92(0.56-15.14) 0.203
TT 1259/1781 1.00 Reference 623/723 1.23(1.07-1.40) 0.002 79/75 1.48(1.07-2.06) 0.019
Combined TC 781/839 1.30(1.15-1.47) 3.28E-05 360/400 1.30(1.10-1.53) 0.002 51/51 1.45(0.97-2.17) 0.068 0.276
CC 104/107 1.32(1.00-1.76) 0.054 47/52 1.31(0.87-1.97) 0.195 13/4 4.62(1.49-14.38) 0.008
Age, gender, smoking and principal components were adjusted when appropriate.
Table S5. Pathway enrichment and GO analysis.
Gene Category Term Count % P Fold a Bonferroni b
KEGG_PATHWAY Olfactory transduction 194 46.6 2.10E-214 14.0 2.00E-212
GO_MF olfactory receptor activity 196 47.1 8.00E-243 23.9 1.50E-240
GO_MF G-protein coupled receptor activity 210 50.5 1.00E-215 15.6 2.00E-213
GO_MF odorant binding 47 11.3 4.10E-55 26.9 7.90E-53
GO_MF transmembrane signaling receptor activity 48 11.5 1.20E-36 11.8 2.40E-34
GO_MF type I interferon receptor binding 8 1.9 1.40E-08 24.7 2.60E-06
GO_MF trace-amine receptor activity 4 1.0 1.30E-04 35.1 2.50E-02
GO_MF adrenergic receptor activity 4 1.0 2.20E-04 30.1 4.20E-02
GO_CC plasma membrane 227 54.6 4.90E-68 2.9 5.50E-66
GO_CC integral component of membrane 240 57.7 5.80E-59 2.5 6.50E-57
GO_CC keratin filament 12 2.9 2.60E-06 6.4 2.90E-04
GO_BP detection of chemical stimulus involved in sensory perception of smell 196 47.1 5.70E-246 24.5 2.80E-243
OPRM1
GO_BP G-protein coupled receptor signaling pathway 204 49.0 2.10E-183 12.1 1.00E-180
GO_BP sensory perception of smell 57 13.7 1.00E-56 19.0 4.90E-54
GO_BP detection of chemical stimulus involved in sensory perception 48 11.5 2.90E-56 26.8 1.50E-53
GO_BP natural killer cell activation involved in immune response 8 1.9 3.20E-08 22.4 1.60E-05
GO_BP positive regulation of peptidyl-serine phosphorylation of STAT protein 8 1.9 3.20E-08 22.4 1.60E-05
GO_BP T cell activation involved in immune response 8 1.9 1.00E-07 19.3 5.00E-05
GO_BP regulation of type I interferon-mediated signaling pathway 8 1.9 3.70E-07 16.4 1.80E-04
GO_BP B cell proliferation 8 1.9 1.70E-06 13.3 8.50E-04
GO_BP response to exogenous dsRNA 8 1.9 2.70E-06 12.5 1.30E-03
GO_BP B cell differentiation 9 2.2 3.10E-05 7.2 1.50E-02
GO_BP adenylate cyclase-activating serotonin receptor signaling pathway 5 1.2 7.60E-05 20.4 3.70E-02
GO_BP humoral immune response 8 1.9 9.00E-05 7.5 4.40E-02
NLRP8 KEGG_PATHWAY Olfactory transduction 176 16.1 3.10E-110 6.7 7.60E-108
 GO_MF olfactory receptor activity 177 16.2 1.00E-111 7.7 9.10E-109
GO_MF G-protein coupled receptor activity 193 17.7 3.30E-85 5.1 2.90E-82
GO_MF odorant binding 45 4.1 1.40E-31 9.1 1.20E-28
GO_MF transmembrane signaling receptor activity 50 4.6 1.80E-18 4.4 1.50E-15
GO_MF type I interferon receptor binding 8 0.7 1.50E-05 8.8 1.30E-02
GO_MF structural molecule activity 31 2.8 2.50E-05 2.3 2.10E-02
GO_CC plasma membrane 379 34.7 1.30E-33 1.7 5.80E-31
GO_CC integral component of membrane 404 37.0 3.50E-21 1.5 1.60E-18
GO_CC extracellular region 127 11.6 3.30E-06 1.5 1.50E-03
GO_BP detection of chemical stimulus involved in sensory perception of smell 177 16.2 1.50E-113 7.8 4.70E-110
GO_BP G-protein coupled receptor signaling pathway 200 18.3 1.80E-72 4.2 5.70E-69
GO_BP sensory perception of smell 57 5.2 1.80E-31 6.7 5.70E-28
GO_BP detection of chemical stimulus involved in sensory perception 45 4.1 5.70E-31 8.9 1.80E-27
GO_BP keratinocyte differentiation 17 1.6 1.90E-06 4.2 6.10E-03
a
Fold enrichment in each pathway or GO process.
b
P values after taking Bonferroni correction.
Supplementary Figure 1. Rs805165 was significantly associated with the expression of AC010525.7 and AC024580.1 in lung tissues based
on GTEx v7 database.
Supplementary Figure 2. Expression of OPRM1 and NLRP8 in 60 paired lung tumor tissues and adjacent normal tissues based on
GSE19804.