Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci
João Fadista, Line Skotte, Juha Karjalainen, Erik Abner, Erik Sørensen, Henrik Ullum, Thomas Werge, iPSYCH Group, Thomas Werge, David M. Hougaard, Anders D. Børglum, Merete Nordentoft, Preben Bo Mortensen, Tõnu Esko, Lili Milani, Aarno Palotie, Mark J. Daly, Mads Melbye, Bjarke Feenstra, Frank Geller
Abstract
Hernias are characterized by protrusion of an organ or tissue through its surrounding cavity and often require surgical repair. In this study we identify 65,492 cases for five hernia types in the UK Biobank and perform genome-wide association study scans for these five types and two combined groups. Our results show associated variants in all scans. Inguinal hernia has the most associations and we conduct a follow-up study with 23,803 additional cases from four study groups giving 84 independently associated variants. Identified variants from all scans are collapsed into 81 independent loci. Further testing shows that 26 loci are associated with more than one hernia type, suggesting substantial overlap between the underlying genetic mechanisms. Pathway analyses identify several genes with a strong link to collagen and/or elastin (ADAMTS6, ADAMTS16, ADAMTSL3, LOX, ELN) in the vicinity of associated loci for inguinal hernia, which substantiates an essential role of connective tissue morphology.