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

被引：51

作者：

Byun, Jinyoung ^{[1
,2
]}

Han, Younghun ^{[1
,2
]}

Li, Yafang ^{[1
,2
,3
]}

Xia, Jun ^{[1
,4
]}

Long, Erping ^{[5
]}

Choi, Jiyeon ^{[5
]}

Xiao, Xiangjun ^{[1
]}

Zhu, Meng ^{[6
]}

Zhou, Wen ^{[1
]}

Sun, Ryan ^{[7
]}

Bosse, Yohan ^{[8
]}

Song, Zhuoyi ^{[1
,4
]}

Schwartz, Ann ^{[9
,10
]}

Lusk, Christine ^{[9
,10
]}

Rafnar, Thorunn ^{[11
]}

Stefansson, Kari ^{[11
]}

Zhang, Tongwu ^{[5
]}

Zhao, Wei ^{[5
]}

Pettit, Rowland W. ^{[1
]}

Liu, Yanhong ^{[2
,3
]}

Li, Xihao ^{[12
]}

Zhou, Hufeng ^{[12
]}

Walsh, Kyle M. ^{[13
]}

Gorlov, Ivan ^{[1
,2
,3
]}

Gorlova, Olga ^{[1
,2
,3
]}

Zhu, Dakai ^{[1
,2
]}

Rosenberg, Susan M. ^{[3
,4
]}

Pinney, Susan ^{[14
]}

Bailey-Wilson, Joan E. ^{[15
]}

Mandal, Diptasri ^{[16
]}

de Andrade, Mariza ^{[17
]}

Gaba, Colette ^{[18
]}

Willey, James C. ^{[18
]}

You, Ming ^{[19
]}

Anderson, Marshall ^{[14
]}

Wiencke, John K. ^{[20
]}

Albanes, Demetrius ^{[5
]}

Lam, Stephan ^{[21
]}

Tardon, Adonina ^{[22
,23
]}

Chen, Chu ^{[24
]}

Goodman, Gary ^{[25
]}

Bojeson, Stig ^{[26
,27
]}

Brenner, Hermann ^{[28
,29
,30
,31
]}

Landi, Maria Teresa ^{[5
]}

Chanock, Stephen J. ^{[5
]}

Johansson, Mattias ^{[32
]}

Muley, Thomas ^{[33
,34
]}

Risch, Angela ^{[33
,34
,35
,36
]}

Wichmann, H-Erich ^{[37
]}

Bickeboeller, Heike ^{[38
]}

机构：

[1] Baylor Coll Med, Inst Clin & Translat Res, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Med, Sect Epidemiol & Populat Sci, Houston, TX 77030 USA

[3] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[5] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[6] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Epidemiol, Nanjing, Peoples R China

[7] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[8] Laval Univ, Inst Univ Cardiol & Pneumol Quebec Univ Laval, Dept Mol Med, Quebec City, PQ, Canada

[9] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA

[10] Karmanos Canc Inst, Detroit, MI USA

[11] deCODE Genet Amgen, Sturlugata 8, Reykjavik, Iceland

[12] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[13] Duke Univ, Duke Canc Inst, Med Ctr, Durham, NC USA

[14] Univ Cincinnati, Coll Med, Cincinnati, OH USA

[15] NHGRI, NIH, Baltimore, MD USA

[16] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA

[17] Mayo Clin, Coll Med, Rochester, MN USA

[18] Univ Toledo, Coll Med & Life Sci, Toledo, OH USA

[19] Houston Methodist Res Inst, Ctr Canc Prevent, Houston, TX USA

[20] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[21] BC Canc, Dept Integrat Oncol, Vancouver, BC, Canada

[22] Univ Oviedo, Publ Hlth Dept, ISPA, Asturias, Spain

[23] CIBERESP, Asturias, Spain

[24] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Publ Hlth Sci Div, Seattle, WA 98104 USA

[25] Swedish Canc Inst, Seattle, WA USA

[26] Copenhagen Univ Hosp, Herlev Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark

[27] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[28] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[29] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[30] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[31] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[32] World Hlth Org, Sect Genet, Int Agcy Res Canc, Lyon, France

[33] DKFZ German Canc Res Ctr, Div Canc Epigen, Heidelberg, Germany

[34] German Ctr Lung Res DZL, Translat Lung Res Ctr Heidelberg TLRC H, Heidelberg, Germany

[35] Univ Salzburg, Allergy Canc BioNano Res Ctr, Dept Biosci & Med Biol, Salzburg, Austria

[36] Canc Cluster Salzburg, Salzburg, Austria

[37] Helmholtz Ctr, Inst Epidemiol, Munich, Germany

[38] Georg August Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, Gottingen, Germany

[39] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[40] Carmel Hosp, Clalit Natl Canc Control Ctr, Haifa, Israel

[41] Technion Fac Med, Haifa, Israel

[42] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA

[43] Univ Liverpool, Dept Mol & Clin Canc Med, Roy Castle Lung Canc Res Programme, Liverpool, Merseyside, England

[44] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[45] Univ Hawaii, Epidemiol Program, Canc Ctr, Honolulu, HI USA

[46] Lund Univ, Fac Med, Lund, Sweden

[47] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[48] Dartmouth Coll, Dept Epidemiol & Community, Hanover, NH 03755 USA

[49] Radboud Univ Nijmegen Med Ctr, Nijmegen, Netherlands

[50] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Peoples R China

来源：

NATURE GENETICS | 2022年 / 54卷 / 08期

基金：

美国国家卫生研究院;

关键词：

EXACT TESTS; ASSOCIATION; VARIANTS; IRF4; RISK; REPLICATION; EXPRESSION; 15Q25; POWER; JOINT;

D O I：

10.1038/s41588-022-01115-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk. 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.

引用

页码：1167 / +

页数：22

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