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

Author

Listed:
  • João Fadista

    (Statens Serum Institut
    Lund University Diabetes Centre
    University of Helsinki)

  • Line Skotte

    (Statens Serum Institut)

  • Juha Karjalainen

    (University of Helsinki
    Broad Institute of MIT and Harvard
    Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School)

  • Erik Abner

    (University of Tartu)

  • Erik Sørensen

    (Copenhagen University Hospital, Rigshospitalet)

  • Henrik Ullum

    (Copenhagen University Hospital, Rigshospitalet
    Statens Serum Institut)

  • Thomas Werge

    (iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of Copenhagen
    University of Copenhagen
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus)

  • Tõnu Esko

    (University of Tartu)

  • Lili Milani

    (University of Tartu)

  • Aarno Palotie

    (University of Helsinki
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Mark Daly

    (University of Helsinki
    Broad Institute of MIT and Harvard)

  • Mads Melbye

    (University of Copenhagen
    Norwegian University of Science and Technology
    Norwegian Institute of Public Health
    Stanford University School of Medicine)

  • Bjarke Feenstra

    (Statens Serum Institut)

  • Frank Geller

    (Statens Serum Institut)

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.

Suggested Citation

  • João Fadista & Line Skotte & Juha Karjalainen & Erik Abner & Erik Sørensen & Henrik Ullum & Thomas Werge & Tõnu Esko & Lili Milani & Aarno Palotie & Mark Daly & Mads Melbye & Bjarke Feenstra & Frank G, 2022. "Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30921-4
    DOI: 10.1038/s41467-022-30921-4
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    References listed on IDEAS

    as
    1. Bryan N Howie & Peter Donnelly & Jonathan Marchini, 2009. "A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-15, June.
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    1. Natàlia Pujol-Gualdo & Kristi Läll & Maarja Lepamets & Henna-Riikka Rossi & Riikka K. Arffman & Terhi T. Piltonen & Reedik Mägi & Triin Laisk, 2022. "Advancing our understanding of genetic risk factors and potential personalized strategies for pelvic organ prolapse," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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