Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
Creators: name: Ahn, Yoon-Ok
name: Chang-Claude, Jenny
name: Mecklin, Jukka-Pekka
name: White, Emily
name: Toland, Amanda
name: Obón-Santacana, Mireia
name: Bézieau, Stéphane
name: Briggs, Sarah E. W.
name: Kim, Andre
name: Hsu, Li
name: Matsuo, Keitaro
name: Shibata, David
name: Qu, Chenxu
name: Platz, Elizabeth A.
name: Ruiz-Narvaez, Edward
name: Kundaje, Anshul
name: Cruz-Correa, Marcia
name: Schmit, Stephanie L.
name: Matsuda, Koichi
name: Schulze, Matthias B.
name: Kerr, Rachel
name: Ulrich, Cornelia M.
name: Bishop, D. Timothy
name: Moratalla-Navarro, Ferran
name: Sakoda, Lori C.
name: Peters, Ulrike
name: Pardini, Barbara
name: Scacheri, Peter C.
name: Lindblom, Annika
name: Castells, Antoni
name: van Guelpen, Bethany
name: Knekt, Paul
name: Yen, Yun
name: Ping, Jie
name: Guo, Xingyi
name: Shu, Xiao-Ou
name: Tomlinson, Ian
name: Win, Aung Ko
name: Conti, David V.
name: Li, Chao
name: Albanes, Demetrius
name: Jung, Keum Ji
name: Palmer, Julie R.
name: FitzGerald, Liesel M.
name: Thomas, Minta
name: Broderick, Peter
name: Newcomb, Polly A.
name: Hayward, Caroline
name: Berndt, Sonja I.
name: Campbell, Peter T.
name: Harris, Sarah E.
name: Gago-Dominguez, Manuela
name: Reid, Stuart
name: Shen, Quanhu
name: Kooperberg, Charles
name: Blackmur, James
name: Cajuso, Tatiana
name: Li, Li
name: Pukkala, Eero
name: Pearlman, Rachel
name: Brezina, Stefanie
name: Rennert, Gad
name: Hopper, John L.
name: Lin, Yi
name: Cai, Qiuyin
name: Yamaji, Taiki
name: Gauderman, W. James
name: Li, Christopher I.
name: Haile, Robert W.
name: Pai, Rish K.
name: Devall, Matthew
name: Shin, Min-Ho
name: Gunter, Marc J.
name: McNeil, Caroline E.
name: Lenz, Heinz-Josef
name: Kerr, David
name: Stadler, Zsofia K.
name: Sherwood, Kitty
name: Svinti, Victoria
name: Gruber, Stephen B.
name: Keku, Temitope O.
name: Wen, Wanqing
name: Castellví-Bel, Sergi
name: Aaltonen, Lauri A.
name: Farrington, Susan M.
name: Duggan, David
name: Qu, Conghui
name: Pugh, Elizabeth
name: Xie, Yuhan
name: Weinstein, Stephanie J.
name: Buchanan, Daniel D.
name: Chan, Andrew T.
name: Shulman, Katerina
name: Feskens, Edith J. M.
name: Casey, Graham
name: McDonnell, Kevin J.
name: Schoen, Robert E.
name: Siegel, Erin
name: Vaughan-Shaw, Peter G.
name: Hampel, Heather
name: Hunter, David J.
name: Su, Yu-Ru
name: Murphy, Neil
name: Timofeeva, Maria N.
name: Larsson, Susanna C.
name: Fernandez-Tajes, Juan
name: Jia, Guochong
name: Thomas, Sushma S.
name: Chen, Zhishan
name: Eriksson, Johan G.
name: Jenkins, Mark A.
name: Zheng, Wei
name: Schafmayer, Clemens
name: Jia, Wei-Hua
name: Giles, Graham G.
name: Arndt, Volker
name: Figueiredo, Jane C.
name: Long, Jirong
name: Coetzee, Gerhard
name: Shin, Aesun
name: Studd, James
name: Ooi, Li Yin
name: Hampe, Jochen
name: Bien, Stephanie A.
name: Rissanen, Harri
name: Gsur, Andrea
name: Vodicka, Pavel
name: Southey, Melissa C.
name: Kondelin, Johanna
name: Tanskanen, Tomas
name: Zhao, Hongyu
name: Brenner, Hermann
name: Houlston, Richard S.
name: Prentice, Ross
name: Renkonen-Sinisalo, Laura
name: Edlund, Christopher K.
name: Lejbkowicz, Flavio
name: Abu-Ful, Zomoroda
name: Cheadle, Jeremy P.
name: Sawada, Norie
name: Kim, Dong-Hyun
name: Markowitz, Sanford
name: Martín-Sánchez, Vicente
name: Gallinger, Steven
name: Offit, Kenneth
name: Fernandez-Rozadilla, Ceres
name: Joshi, Amit D.
name: Steinfelder, Robert
name: Palles, Claire
name: Pharoah, Paul D. P.
name: Donnelly, Kevin
name: Schumacher, Fredrick R.
name: Slattery, Martha L.
name: Iwasaki, Motoki
name: Doheny, Kimberly F.
name: Chanock, Stephen J.
name: Vymetalkova, Veronika
name: Tsilidis, Kostas K.
name: Kirac, Iva
name: Wu, Anna H.
name: Kim, Jeongseon
name: Ren, Zefang
name: Shelford, Tameka
name: Greenson, Joel K.
name: Böhm, Jan
name: Moreno, Victor
name: Tanikawa, Chizu
name: Jousilahti, Pekka
name: Martinez, Marie Elena
name: Gao, Yu-Tang
name: Idos, Gregory E.
name: Palin, Kimmo
name: Hudson, Thomas J.
name: Hayes, Richard B.
name: Moreira, Leticia
name: Lee, Soo Chin
name: Männistö, Satu
name: Díez-Obrero, Virginia
name: Kaplan, Richard
name: Visvanathan, Kala
name: Shcherbina, Anna
name: Theodoratou, Evropi
name: Tao, Ran
name: Lau, Ken S.
name: Oze, Isao
name: Walker, Marion
name: Ogino, Shuji
name: Wolk, Alicja
name: Melas, Marilena
name: Woods, Michael O.
name: Law, Philip J.
name: Hänninen, Ulrika
name: Huyghe, Jeroen R.
name: Vodickova, Ludmila
name: Harrison, Tabitha A.
name: Jee, Sun Ha
name: Potter, John D.
name: Le Marchand, Loic
name: Hoffmeister, Michael
name: Kweon, Sun-Seog
name: Lu, Yingchang
name: van Duijnhoven, Franzel
name: Oh, Jae Hwan
name: Dunlop, Malcolm G.
name: Deary, Ian J.
Publisher: name: Springer Nature
Year: 2024

description: Genome-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.