Chen ZGuo XTao RHuyghe JRLaw PJFernandez-Rozadilla CPing JJia GLong JLi CShen QXie YTimofeeva MNThomas MSchmit SLDíez-Obrero VDevall MMoratalla-Navarro FFernandez-Tajes JPalles CSherwood KBriggs SEWSvinti VDonnelly KFarrington SMBlackmur JVaughan-Shaw PGShu X-OLu YBroderick PStudd JHarrison TAConti DVSchumacher FRMelas MRennert GObón-Santacana MMartín-Sánchez VOh JHKim JJee SHJung KJKweon S-SShin M-HShin AAhn Y-OKim D-HOze IWen WMatsuo KMatsuda KTanikawa CRen ZGao Y-TJia W-HHopper JLJenkins MAWin AKPai RKFigueiredo JCHaile RWGallinger SWoods MONewcomb PADuggan DCheadle JPKaplan RKerr RKerr DKirac IBöhm JMecklin J-PJousilahti PKnekt PAaltonen LARissanen HPukkala EEriksson JGCajuso THänninen UKondelin JPalin KTanskanen TRenkonen-Sinisalo LMännistö SAlbanes DWeinstein SJRuiz-Narvaez EPalmer JRBuchanan DDPlatz EAVisvanathan KUlrich CMSiegel EBrezina SGsur ACampbell PTChang-Claude JHoffmeister MBrenner HSlattery MLPotter JDTsilidis KKSchulze MBGunter MJMurphy NCastells ACastellví-Bel SMoreira LArndt VShcherbina ABishop DTGiles GGSouthey MCIdos GEMcDonnell KJAbu-Ful ZGreenson JKShulman KLejbkowicz FOffit KSu Y-RSteinfelder RKeku TOvan Guelpen BHudson TJHampel HPearlman RBerndt SIHayes RBMartinez METhomas SSPharoah PDPLarsson SCYen YLenz H-JWhite ELi LDoheny KFPugh EShelford TChan ATCruz-Correa MLindblom AHunter DJJoshi ADSchafmayer CScacheri PCKundaje ASchoen REHampe JStadler ZKVodicka PVodickova LVymetalkova VEdlund CKGauderman WJShibata DToland AMarkowitz SKim AChanock SJvan Duijnhoven FFeskens EJMSakoda LCGago-Dominguez MWolk APardini BFitzGerald LMLee SCOgino SBien SAKooperberg CLi CILin YPrentice RQu CBézieau SYamaji TSawada NIwasaki MLe Marchand LWu AHQu CMcNeil CECoetzee GHayward CDeary IJHarris SETheodoratou EReid SWalker MOoi LYLau KSZhao HHsu LCai QDunlop MGGruber SBHoulston RSMoreno VCasey GPeters UTomlinson IZheng W2024-05-092024-05-092024-04-26Chen Z, Guo X, Tao R, Huyghe JR, Law PJ, Fernandez-Rozadilla C, Ping J, Jia G, Long J, Li C, Shen Q, Xie Y, Timofeeva MN, Thomas M, Schmit SL, Díez-Obrero V, Devall M, Moratalla-Navarro F, Fernandez-Tajes J, Palles C, Sherwood K, Briggs SEW, Svinti V, Donnelly K, Farrington SM, Blackmur J, Vaughan-Shaw PG, Shu X-O, Lu Y, Broderick P, Studd J, Harrison TA, Conti DV, Schumacher FR, Melas M, Rennert G, Obón-Santacana M, Martín-Sánchez V, Oh JH, Kim J, Jee SH, Jung KJ, Kweon S-S, Shin M-H, Shin A, Ahn Y-O, Kim D-H, Oze I, Wen W, Matsuo K, Matsuda K, Tanikawa C, Ren Z, Gao Y-T, Jia W-H, Hopper JL, Jenkins MA, Win AK, Pai RK, Figueiredo JC, Haile RW, Gallinger S, Woods MO, Newcomb PA, Duggan D, Cheadle JP, Kaplan R, Kerr R, Kerr D, Kirac I, Böhm J, Mecklin J-P, Jousilahti P, Knekt P, Aaltonen LA, Rissanen H, Pukkala E, Eriksson JG, Cajuso T, Hänninen U, Kondelin J, Palin K, Tanskanen T, Renkonen-Sinisalo L, Männistö S, Albanes D, Weinstein SJ, Ruiz-Narvaez E, Palmer JR, Buchanan DD, Platz EA, Visvanathan K, Ulrich CM, Siegel E, Brezina S, Gsur A, Campbell PT, Chang-Claude J, Hoffmeister M, Brenner H, Slattery ML, Potter JD, Tsilidis KK, Schulze MB, Gunter MJ, Murphy N, Castells A, Castellví-Bel S, Moreira L, Arndt V, Shcherbina A, Bishop DT, Giles GG, Southey MC, Idos GE, McDonnell KJ, Abu-Ful Z, Greenson JK, Shulman K, Lejbkowicz F, Offit K, Su Y-R, Steinfelder R, Keku TO, van Guelpen B, Hudson TJ, Hampel H, Pearlman R, Berndt SI, Hayes RB, Martinez ME, Thomas SS, Pharoah PDP, Larsson SC, Yen Y, Lenz H-J, White E, Li L, Doheny KF, Pugh E, Shelford T, Chan AT, Cruz-Correa M, Lindblom A, Hunter DJ, Joshi AD, Schafmayer C, Scacheri PC, Kundaje A, Schoen RE, Hampe J, Stadler ZK, Vodicka P, Vodickova L, Vymetalkova V, Edlund CK, Gauderman WJ, Shibata D, Toland A, Markowitz S, Kim A, Chanock SJ, van Duijnhoven F, Feskens EJM, Sakoda LC, Gago-Dominguez M, Wolk A, Pardini B, FitzGerald LM, Lee SC, Ogino S, Bien SA, Kooperberg C, Li CI, Lin Y, Prentice R, Qu C, Bézieau S, Yamaji T, Sawada N, Iwasaki M, Le Marchand L, Wu AH, Qu C, McNeil CE, Coetzee G, Hayward C, Deary IJ, Harris SE, Theodoratou E, Reid S, Walker M, Ooi LY, Lau KS, Zhao H, Hsu L, Cai Q, Dunlop MG, Gruber SB, Houlston RS, Moreno V, Casey G, Peters U, Tomlinson I, Zheng W. (2024). Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.. Nat Commun. 15. 1. (pp. 3557-).0028-0836https://mro.massey.ac.nz/handle/10179/69532Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.(c) 2024 The Author/sCC BY 4.0https://creativecommons.org/licenses/by/4.0/HumansColorectal NeoplasmsGenetic Predisposition to DiseaseGenome-Wide Association StudyAsian PeopleWhite PeoplePolymorphism, Single NucleotideQuantitative Trait LociExome SequencingCase-Control StudiesTranscriptomeChromosome MappingMaleFemaleEast Asian PeopleJournal article10.1038/s41467-024-47399-x2041-1723journal-article3557-https://www.ncbi.nlm.nih.gov/pubmed/38670944355710.1038/s41467-024-47399-x