Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci

Hernias are characterized by protrusion of an organ or tissue through its surrounding cavity and often require surgical repair. We identified 65,492 cases for five hernia types in the UK Biobank and performed genome-wide association study scans for these five types and two combined groups. The results showed associated variants in all scans. Inguinal hernia had the most associations and we conducted a replication study with 23,803 additional cases from four study groups giving 84 independently associated variants. Identified variants from all scans were collapsed into 81 independent loci. Further testing showed that 26 loci were associated with more than one hernia type, suggesting substantial overlap between the underlying genetic mechanisms. Pathway analysis identified 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.