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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

ABSTRACT: To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.

SUBMITTER: Byun J

PROVIDER: S-EPMC9373844 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

Byun Jinyoung J Han Younghun Y Li Yafang Y Xia Jun J Long Erping E Choi Jiyeon J Xiao Xiangjun X Zhu Meng M Zhou Wen W Sun Ryan R Bossé Yohan Y Song Zhuoyi Z Schwartz Ann A Lusk Christine C Rafnar Thorunn T Stefansson Kari K Zhang Tongwu T Zhao Wei W Pettit Rowland W RW Liu Yanhong Y Li Xihao X Zhou Hufeng H Walsh Kyle M KM Gorlov Ivan I Gorlova Olga O Zhu Dakai D Rosenberg Susan M SM Pinney Susan S Bailey-Wilson Joan E JE Mandal Diptasri D de Andrade Mariza M Gaba Colette C Willey James C JC You Ming M Anderson Marshall M Wiencke John K JK Albanes Demetrius D Lam Stephan S Tardon Adonina A Chen Chu C Goodman Gary G Bojeson Stig S Brenner Hermann H Landi Maria Teresa MT Chanock Stephen J SJ Johansson Mattias M Muley Thomas T Risch Angela A Wichmann H-Erich HE Bickeböller Heike H Christiani David C DC Rennert Gad G Arnold Susanne S Field John K JK Shete Sanjay S Le Marchand Loic L Melander Olle O Brunnstrom Hans H Liu Geoffrey G Andrew Angeline S AS Kiemeney Lambertus A LA Shen Hongbing H Zienolddiny Shanbeh S Grankvist Kjell K Johansson Mikael M Caporaso Neil N Cox Angela A Hong Yun-Chul YC Yuan Jian-Min JM Lazarus Philip P Schabath Matthew B MB Aldrich Melinda C MC Patel Alpa A Lan Qing Q Rothman Nathaniel N Taylor Fiona F Kachuri Linda L Witte John S JS Sakoda Lori C LC Spitz Margaret M Brennan Paul P Lin Xihong X McKay James J Hung Rayjean J RJ Amos Christopher I CI

Nature genetics 20220801 8

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHR ...[more]

PMID: 35915169

Dataset Information

Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

Publications

Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

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