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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1167-1177
Number of pages11
JournalNature Genetics
Volume54
Issue number8
DOIs
StatePublished - Aug 2022

ASJC Scopus subject areas

  • Genetics

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