Publication: 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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Date
2022-08
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Springer Science and Business Media LLC
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Byun, Jinyoung, Younghun Han, Yafang Li, Jun Xia, Erping Long, Jiyeon Choi, Xiangjun Xiao et al. "Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer." Nat Genet 54, no. 8 (2022): 1167-1177. DOI: 10.1038/s41588-022-01115-x
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Abstract
To identify novel genetic associations to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, Asian, and African populations and discovered five novel 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. Further, fine-mapping and eQTL 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.
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Full list of authors:
Jinyoung Byun1,2†,
Younghun Han1,2†,
Yafang Li1-3†,
Jun Xia1,4†,
Erping Long5†,
Jiyeon Choi5,
Xiangjun Xiao1,
Meng Zhu6,
Wen Zhou1,
Ryan Sun7,
Yohan Bossé8,
Zhuoyi Song1,4,
Ann Schwartz9,10,
Christine Lusk9,10,
Thorunn Rafnar11,
Kari Stefansson11,
Tongwu Zhang5,
Wei Zhao5,
Rowland W Pettit1,
Yanhong Liu2,3,
Xihao Li12,
Hufeng Zhou12,
Kyle M. Walsh13,
Ivan Gorlov1-3,
Olga Gorlova1-3,
Dakai Zhu1,2,
Susan M Rosenberg3,4,
Susan Pinney14,
Joan E. Bailey-Wilson15,
Diptasri Mandal16,
Mariza de Andrade17,
Colette Gaba18,
James C. Willey18,
Ming You19,
Marshall Anderson14,
John K. Wiencke20,
Demetrius Albanes5,
Stephan Lam21,
Adonina Tardon22,
Chu Chen23,
Gary Goodman24,
Stig Bojeson25,26,
Hermann Brenner27-29,
Maria Teresa Landi5,
Stephen J. Chanock5,
Mattias Johansson30,
Thomas Muley31,32,
Angela Risch31-33,
H.-Erich Wichmann34,
Heike Bickeböller35,
David C. Christiani36,
Gad Rennert37,
Susanne Arnold38,
John K. Field39,
Sanjay Shete7,40,
Loic Le Marchand41,
Olle Melander42,
Hans Brunnstrom42,
Geoffrey Liu43,
Angeline S. Andrew44,
Lambertus A. Kiemeney45,
Hongbing Shen46,
Shanbeh Zienolddiny47,
Kjell Grankvist48,
Mikael Johansson49,
Neil Caporaso5,
Angela Cox50,
Yun-Chul Hong51,
Jian-Min Yuan52,
Philip Lazarus53,
Matthew B. Schabath54,
Melinda C. Aldrich55,
Alpa Patel56,
Qing Lan5,
Nathaniel Rothman5,
Fiona Taylor50,
Linda Kachuri57,
John S. Witte58,
Lori C. Sakoda59,
Margaret Spitz2,
Paul Brennan30,
Xihong Lin12,
James McKay30,
Rayjean J. Hung60,61,
Christopher I. Amos1-3*
INTEGRAL-ILCCO Consortium
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Keywords
Genetics
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