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.
medRxiv : the preprint server for health sciences. 2026 Mar 20*** epublish ***
Elisa Moreno, Nikhil Arora, Emily Bertucci-Richter, Reyhane Eghtedarian, Aristomo Andries, Laurent F Thomas, Julie Horn, Signe N Stafne, Sweta Pathak, FinnGen , Snehal Patil, Dagny Gulla, Hanna M Ollila, David M Evans, Giulia M Ippolito, Wei Zhou, Eivind Coward, Kristian Hveem, Ida Surakka, Marta R Moksnes, Brooke N Wolford, Ben M Brumpton