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

Fadista, JoãoLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Danish Serum Institute, Copenhagen (author)

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.

Skotte, LineDanish Serum Institute, Copenhagen (author)
Karjalainen, JuhaMassachusetts General Hospital,University of Helsinki,Broad Institute (author)
Abner, ErikUniversity of Tartu (author)
Sørensen, ErikCopenhagen University Hospital (author)
Ullum, HenrikCopenhagen University Hospital,Danish Serum Institute, Copenhagen (author)
Werge, ThomasUniversity of Copenhagen (author)
Esko, TõnuUniversity of Tartu (author)
Milani, LiliUniversity of Tartu (author)
Palotie, AarnoMassachusetts General Hospital,University of Helsinki,Broad Institute(Swepub:lu)med-aop (author)
Daly, MarkUniversity of Helsinki,Broad Institute(Swepub:lu)med-mkd (author)
Melbye, MadsNorwegian Institute of Public Health,University of Copenhagen,Stanford University School of Medicine,Norwegian University of Science and Technology (author)
Feenstra, BjarkeDanish Serum Institute, Copenhagen (author)
Geller, FrankDanish Serum Institute, Copenhagen (author)
Translationell muskelforskningForskargrupper vid Lunds universitet (creator_code:org_t)
iPSYCH Group
FinnGen Consortium

By the author/editor: Fadista, João; Skotte, Line; Karjalainen, Juh ...; Abner, Erik; Sørensen, Erik; Ullum, Henrik; show more...; Werge, Thomas; Esko, Tõnu; Milani, Lili; Palotie, Aarno; Daly, Mark; Melbye, Mads; Feenstra, Bjarke; Geller, Frank; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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