Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10130
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Funding
- National Institutes of Health [RC2 AG036607]
- Robert Wood Johnson Foundation
- Ellison Medical Foundation
- Wayne and Gladys Valley Foundation
- Kaiser Permanente
- National Human Genome Research Institute of the National Institutes of Health [R44HG006981]
- NIDDK [1R01DK090382]
- NINDS [1R01NS079231]
- NCI [1R01CA197139]
- Jane Coffin Childs Postdoctoral Fellowship
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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.
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