Genome-wide association meta-analyses over one million individuals identify 54 loci associated with urinary incontinence and its subtypes
Urinary incontinence (UI) markedly reduces quality of life, and its genetic basis remains to be elucidated. Here, we performed GWAS meta-analyses of four UI phenotypes, using hospital-based data from 1,045,436 individuals from the Trøndelag Health Study (HUNT), UK Biobank, FinnGen, and the Michigan Genomics Initiative, and self-reported UI from 56,957 females from HUNT and the Nurses' Health Study. We identified 54 (52 novels) genetic loci associated with at least one UI phenotype. Analyses revealed tissue-specific involvement, with connective and muscular tissues for stress UI, and neural tissues for urge UI, and supported key roles of SUI-prioritized genes in the extracellular matrix organization and muscle function. Further, genetic variations contributes to UI through inflammation, immune, and aging pathways. We identified smoking, higher BMI, higher parity, and pelvic organ prolapse as causal risk factors for UI in females, and benign prostatic hyperplasia in males. Our findings identify key genetic factors, tissues, pathways, and causal underlying UI.
Authors
- Signe Nilssen Stafne (ORCID: https://orcid.org/0000-0003-4922-477X)
- Sweta Pathak
- Emily M. Bertucci (ORCID: https://orcid.org/0000-0002-8348-0024)
- Ida Surakka (ORCID: https://orcid.org/0000-0002-6669-5541)
- Julie Horn (ORCID: https://orcid.org/0000-0003-1344-9707)
- K. Hveem
- Reyhane Eghtedarian (ORCID: https://orcid.org/0000-0002-7603-0009)
- Nikhil Arora (ORCID: https://orcid.org/0000-0001-5767-5410)
- Snehal Patil (ORCID: https://orcid.org/0000-0002-5362-5341)
- D. Gareth Evans (ORCID: https://orcid.org/0000-0002-8482-5784)
- Marta R. Moksnes (ORCID: https://orcid.org/0000-0002-2690-5153)
- Aristomo Andries (ORCID: https://orcid.org/0000-0002-5687-5856)
- Wei Zhou (ORCID: https://orcid.org/0000-0001-7534-3065)
- L T Laurent Thomas
- Hanna M Ollila
- Eivind Coward
- Dagny Gulla
- Ben M Brumpton
- Brooke N Wolford
- FinnGen
- Elisa Moreno
Institutions
- Broad Institute (US)
- Translational Research Institute (AU)
- University of Helsinki (FI)
- Harvard University (US)
- The University of Queensland (AU)
- Norwegian University of Science and Technology (NO)
- University of Michigan (US)
- Levanger Hospital (NO)
- University of Bristol (GB)
- Massachusetts General Hospital (US)
- St Olav's University Hospital (NO)
- Finland University (FI)
- Kristiansund Sykehus (NO)
- Institute for Molecular Medicine Finland (FI)
- Center for Systems Biology (US)
- MRC Epidemiology Unit (GB)
Publication Details
- Journal
- medRxiv
- Published
- 2026-03-13
- DOI
- https://doi.org/10.64898/2026.03.12.26346952
- Primary Topic
- Pelvic floor disorders treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Norges Teknisk-Naturvitenskapelige Universitet
- European Commission
- Kela
- Helse Midt-Norge
- Norges Forskningsråd
- St. Olavs Hospital Universitetssykehuset i Trondheim
- National Institutes of Health
- Medical School, University of Michigan
- HORIZON EUROPE Framework Programme
- Faculty of Medicine and Health, University of Sydney
- Norwegian Institute of Public Health