A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia

被引：81

作者：

Jorgenson, Eric ^{[1
]}

Makki, Nadja ^{[2
,3
]}

Shen, Ling ^{[1
]}

Chen, David C. ^{[4
]}

Tian, Chao ^{[5
]}

Eckalbar, Walter L. ^{[2
,3
]}

Hinds, David ^{[5
]}

Ahituv, Nadav ^{[2
,3
]}

Avins, Andrew ^{[1
]}

机构：

[1] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA

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

[3] UCSF, Inst Human Genet, San Francisco, CA 94158 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Lichtenstein Hernia Clin, Los Angeles, CA 90095 USA

[5] 23andMe Inc, Mountain View, CA 94041 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

美国国家卫生研究院;

关键词：

CONGENITAL DIAPHRAGMATIC-HERNIA; GENETIC EPIDEMIOLOGY RESEARCH; ABDOMINAL AORTIC-ANEURYSM; EHLERS-DANLOS-SYNDROME; AGING GERA COHORT; GENOTYPE IMPUTATION; RISK-FACTORS; WILMS-TUMOR; CONNECTIVE-TISSUE; MEACHAM-SYNDROME;

D O I：

10.1038/ncomms10130

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment.

引用

页数：9

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