1. Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
- Author
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Shi J, Shiraishi K, Choi J, Matsuo K, Chen TY, Dai J, Hung RJ, Chen K, Shu XO, Kim YT, Landi MT, Lin D, Zheng W, Yin Z, Zhou B, Song B, Wang J, Seow WJ, Song L, Chang IS, Hu W, Chien LH, Cai Q, Hong YC, Kim HN, Wu YL, Wong MP, Richardson BD, Funderburk KM, Li S, Zhang T, Breeze C, Wang Z, Blechter B, Bassig BA, Kim JH, Albanes D, Wong JYY, Shin MH, Chung LP, Yang Y, An SJ, Zheng H, Yatabe Y, Zhang XC, Kim YC, Caporaso NE, Chang J, Ho JCM, Kubo M, Daigo Y, Song M, Momozawa Y, Kamatani Y, Kobayashi M, Okubo K, Honda T, Hosgood DH, Kunitoh H, Patel H, Watanabe SI, Miyagi Y, Nakayama H, Matsumoto S, Horinouchi H, Tsuboi M, Hamamoto R, Goto K, Ohe Y, Takahashi A, Goto A, Minamiya Y, Hara M, Nishida Y, Takeuchi K, Wakai K, Matsuda K, Murakami Y, Shimizu K, Suzuki H, Saito M, Ohtaki Y, Tanaka K, Wu T, Wei F, Dai H, Machiela MJ, Su J, Kim YH, Oh IJ, Lee VHF, Chang GC, Tsai YH, Chen KY, Huang MS, Su WC, Chen YM, Seow A, Park JY, Kweon SS, Chen KC, Gao YT, Qian B, Wu C, Lu D, Liu J, Schwartz AG, Houlston R, Spitz MR, Gorlov IP, Wu X, Yang P, Lam S, Tardon A, Chen C, Bojesen SE, Johansson M, Risch A, Bickeböller H, Ji BT, Wichmann HE, Christiani DC, Rennert G, Arnold S, Brennan P, McKay J, Field JK, Shete SS, Le Marchand L, Liu G, Andrew A, Kiemeney LA, Zienolddiny-Narui S, Grankvist K, Johansson M, Cox A, Taylor F, Yuan JM, Lazarus P, Schabath MB, Aldrich MC, Jeon HS, Jiang SS, Sung JS, Chen CH, Hsiao CF, Jung YJ, Guo H, Hu Z, Burdett L, Yeager M, Hutchinson A, Hicks B, Liu J, Zhu B, Berndt SI, Wu W, Wang J, Li Y, Choi JE, Park KH, Sung SW, Liu L, Kang CH, Wang WC, Xu J, Guan P, Tan W, Yu CJ, Yang G, Sihoe ADL, Chen Y, Choi YY, Kim JS, Yoon HI, Park IK, Xu P, He Q, Wang CL, Hung HH, Vermeulen RCH, Cheng I, Wu J, Lim WY, Tsai FY, Chan JKC, Li J, Chen H, Lin HC, Jin L, Liu J, Sawada N, Yamaji T, Wyatt K, Li SA, Ma H, Zhu M, Wang Z, Cheng S, Li X, Ren Y, Chao A, Iwasaki M, Zhu J, Jiang G, Fei K, Wu G, Chen CY, Chen CJ, Yang PC, Yu J, Stevens VL, Fraumeni JF Jr, Chatterjee N, Gorlova OY, Hsiung CA, Amos CI, Shen H, Chanock SJ, Rothman N, Kohno T, and Lan Q
- Subjects
- Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Asia, Eastern epidemiology, Polymorphism, Single Nucleotide, Adenocarcinoma of Lung genetics, Lung Neoplasms epidemiology, Lung Neoplasms genetics
- Abstract
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P
interaction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)- Published
- 2023
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