Genome Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence

BACKGROUND: Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence. METHODS: We carried out a discovery stage case control GWAS in three independent discovery cohorts of European women (n=8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in six additional studies of European ancestry (n=4,069). We collected bladder biopsies from women with incontinence to further investigate bladder expression of implicated genes and pathways (n=50) and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models in METAL, and whole transcriptome analyses using Affymetrix arrays, with replication with TaqMan PCR. RESULTS: In the discovery stage we identified 16 single nucleotide polymorphisms (SNPs) genotyped or imputed at five loci that reached genome-wide significance (p