Ancestry- and sex-specific effects underlying inguinal hernia susceptibility identified in a multiethnic genome-wide association study meta-analysis

被引：7

作者：

Choquet, Helene ^{[1
]}

Li, Weiyu ^{[2
]}

Yin, Jie ^{[1
]}

Bradley, Rachael ^{[2
]}

Hoffmann, Thomas J. ^{[3
,4
]}

Nandakumar, Priyanka ^{[5
]}

Mostaedi, Rouzbeh ^{[6
]}

Tian, Chao ^{[5
]}

Ahituv, Nadav ^{[2
,3
]}

Jorgenson, Eric ^{[7
]}

机构：

[1] Kaiser Permanente Northern Calif KPNC, Div Res, Oakland, CA 94612 USA

[2] Univ Calif San Francisco UCSF, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA

[3] UCSF, Inst Human Genet, San Francisco, CA 94143 USA

[4] UCSF, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA

[5] 23andMe Inc, Sunnyvale, CA 94086 USA

[6] KPNC, Richmond Med Ctr, Richmond, CA 94801 USA

[7] Regeneron Genet Ctr, Tarrytown, NY 10591 USA

来源：

HUMAN MOLECULAR GENETICS | 2022年 / 31卷 / 13期

关键词：

OCCUPATIONAL MECHANICAL EXPOSURES; GENETIC EPIDEMIOLOGY RESEARCH; RISK-FACTORS; ADULT HEALTH; HERITABILITY; RACE/ETHNICITY; ANNOTATION; IMPUTATION; ENHANCERS; COVERAGE;

D O I：

10.1093/hmg/ddac003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inguinal hernias are some of the most frequently diagnosed conditions in clinical practice and inguinal hernia repair is the most common procedure performed by general surgeons. Studies of inguinal hernias in non-European populations are lacking, though it is expected that such studies could identify novel loci. Further, the cumulative lifetime incidence of inguinal hernia is nine times greater in men than women, however, it is not clear why this difference exists. We conducted a genome-wide association meta-analysis of inguinal hernia risk across 513 120 individuals (35 774 cases and 477 346 controls) of Hispanic/Latino, African, Asian and European descent, with replication in 728 418 participants (33 491 cases and 694 927 controls) from the 23andMe, Inc dataset. We identified 63 genome-wide significant loci (P < 5 x 10(-8)), including 41 novel. Ancestry-specific analyses identified two loci (LYPLAL1-AS1/SLC30A10 and STXBP6-NOVA1) in African ancestry individuals. Sex-stratified analyses identified two loci (MYO1D and ZBTB7C) that are specific to women, and four (EBF2, EMX2/RAB11FIP2, VCL and FAM9A/FAM9B) that are specific to men. Functional experiments demonstrated that several of the associated regions (EFEMP1 and LYPLAL1-SLC30A10) function as enhancers and show differential activity between risk and reference alleles. Our study highlights the importance of large-scale genomic studies in ancestrally diverse populations for identifying ancestry-specific inguinal hernia susceptibility loci and provides novel biological insights into inguinal hernia etiology.

引用

页码：2279 / 2293

页数：15

共 37 条

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共 37 条

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Yokoyama, J. S. ;

McGrath, P. J. ;

Peters, E. J. ;

Scheftner, W. A. ;

Coryell, W. ;

Lawson, W. B. ;

Jancic, D. ;

Gejman, P. V. ;

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Zheng, Sean L. ;

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Gratton, Jasmine ;

Bond, Isabelle ;

Roselli, Carolina ;

Miller, David ;

Chopade, Sandesh ;

Schmidt, A. Floriaan ;

Abner, Erik ;

Adams, Lance ;

Andersson, Charlotte ;

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Arnlov, Johan ;

Asselin, Geraldine ;

Raja, Anna Axelsson ;

Backman, Joshua D. ;

Bartz, Traci M. ;

Biddinger, Kiran J. ;

Biggs, Mary L. ;

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Boersma, Eric ;

Brandimarto, Jeffrey ;

Brown, Michael R. ;

Brunak, Soren ;

Bruun, Mie Topholm ;

Buckbinder, Leonard ;

Bundgaard, Henning ;

Carey, David J. ;

Chasman, Daniel I. ;

Chen, Xing ;

Cook, James P. ;

Czuba, Tomasz ;

de Denus, Simon ;

Dehghan, Abbas ;

Delgado, Graciela E. ;

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Karassa, Fotini B. ;

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Akune, Toru ;

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Engstrom, Gunnar ;

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Halldorsson, Bjarni V. ;

Hammond, Christina L. ;

Hart, Deborah J. ;

Helgadottir, Hafdis ;

Hofman, Albert ;

Ikegawa, Shiro ;

Ingvarsson, Thorvaldur ;

Jiang, Qing ;

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Kaprio, Jaakko ;

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Kujala, Urho M. ;

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Ollier, William E. R. ;

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van de Putte, Tom ;

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Gu, Dongfeng ;

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Sim, Xueling ;

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He, Yunfeng ;

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Raffel, Leslie J. ;

Moon, Sanghoon ;

Rotter, Jerome I. ;

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Wu, Tangchun ;

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Wu, Jer-Yuarn ;

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Li, Boyang ;

McGinnis, Kathleen A. ;

Vickers-Smith, Rachel ;

Dao, Cecilia ;

Sun, Ning ;

Kember, Rachel L. ;

Zhou, Hang ;

Becker, William C. ;

Gelernter, Joel ;

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Tanskanen, Tomas ;

van den Berg, Linda ;

Valimaki, Niko ;

Aavikko, Mervi ;

Ness-Jensen, Eivind ;

Hveem, Kristian ;

Wettergren, Yvonne ;

Lindskog, Elinor Bexe ;

Tonisson, Neeme ;

Metspalu, Andres ;

Silander, Kaisa ;

Orlando, Giulia ;

Law, Philip J. ;

Tuupanen, Sari ;

Gylfe, Alexandra E. ;

Hanninen, Ulrika A. ;

Cajuso, Tatiana ;

Kondelin, Johanna ;

Sarin, Antti-Pekka ;

Pukkala, Eero ;

Jousilahti, Pekka ;

Salomaa, Veikko ;

Ripatti, Samuli ;

Palotie, Aarno ;

Jarvinen, Heikki ;

Renkonen-Sinisalo, Laura ;

Lepisto, Anna ;

Bohm, Jan ;

Mecklin, Jukka-Pekka ;

Al-Tassan, Nada A. ;

Palles, Claire ;

Martin, Lynn ;

Barclay, Ella ;

Tenesa, Albert ;

Farrington, Susan M. ;

Timofeeva, Maria N. ;

Meyer, Brian F. ;

Wakil, Salma M. ;

Campbell, Harry ;

Smith, Christopher G. ;

Idziaszczyk, Shelley ;

Maughan, Tim S. ;

Kaplan, Richard ;

Kerr, Rachel ;

Kerr, David ;

Buchanan, Daniel D. ;

Win, Aung K. ;

Hopper, John ;

Jenkins, Mark A. ;

Newcomb, Polly A. .

INTERNATIONAL JOURNAL OF CANCER, 2018, 142 (03) :540-546

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Keene, Keith L. ;

Hyacinth, Hyacinth I. ;

Bis, Joshua C. ;

Kittner, Steven J. ;

Mitchell, Braxton D. ;

Cheng, Yu-Ching ;

Pare, Guillaume ;

Chong, Michael ;

O'Donnell, Martin ;

Meschia, James F. ;

Chen, Wei-Min ;

Sale, Michele M. ;

Rich, Stephen S. ;

Nalls, Mike A. ;

Zonderman, Alan B. ;

Evans, Michele K. ;

Wilson, James G. ;

Correa, Adolfo ;

Markus, Hugh S. ;

Traylor, Matthew ;

Lewis, Cathryn M. ;

Carty, Cara L. ;

Reiner, Alexander ;

Haessler, Jeff ;

Langefeld, Carl D. ;

Gottesman, Rebecca ;

Mosley, Thomas H. ;

Woo, Daniel ;

Yaffe, Kristine ;

Liu, YongMei ;

Longstreth, William T. ;

Psaty, Bruce M. ;

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