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

Collagen / metabolism Follow-Up Studies Genome-Wide Association Study Hernia, Inguinal / genetics Humans

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
09 06 2022
Historique:
received: 07 05 2021
accepted: 18 05 2022
entrez: 10 6 2022
pubmed: 11 6 2022
medline: 14 6 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-022-30921-4 PMID: 35680855 PMC: PMC9184475
pubmed: 35680855
doi: 10.1038/s41467-022-30921-4
pii: 10.1038/s41467-022-30921-4
pmc: PMC9184475
doi:

Substances chimiques

Collagen 9007-34-5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3200

Investigateurs

Thomas Werge (T)
David M Hougaard (DM)
Anders D Børglum (AD)
Merete Nordentoft (M)
Preben B Mortensen (PB)

Informations de copyright

© 2022. The Author(s).

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Auteurs

João Fadista (J)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden.
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.

Line Skotte (L)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
ORCID: 0000-0002-7398-1271

Juha Karjalainen (J)

Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Erik Abner (E)

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.
ORCID: 0000-0002-6529-3161

Erik Sørensen (E)

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Henrik Ullum (H)

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Statens Serum Institut, Copenhagen, Denmark.

Thomas Werge (T)

iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Lundbeck Foundation Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Aarhus, Denmark.
ORCID: 0000-0003-1829-0766

Tõnu Esko (T)

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.

Lili Milani (L)

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.
ORCID: 0000-0002-5323-3102

Aarno Palotie (A)

Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Analytic and Translational Genetics Unit, Department of Medicine, and the Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0002-2527-5874

Mark Daly (M)

Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Mads Melbye (M)

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
K.G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway.
Norwegian Institute of Public Health, Oslo, Norway.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
ORCID: 0000-0001-8264-6785

Bjarke Feenstra (B)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
ORCID: 0000-0003-1478-649X

Frank Geller (F)

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. fge@ssi.dk.
ORCID: 0000-0002-9238-3269

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Classifications MeSH

Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Comprehensive genome-wide association study of...
Recherchemedicale.com › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études de suivi › Comprehensive genome-wide association study of...
Recherchemedicale.com › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Comprehensive genome-wide association study of...
Recherchemedicale.com › États, signes et symptômes pathologiques › États anatomopathologiques › Hernie › Hernie abdominale › Hernie inguinale › Comprehensive genome-wide association study of...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Comprehensive genome-wide association study of...