Genome-Wide Associations with Urinary Incontinence in Women: Case-Control Study

The objective was to determine the genetic variants associated with urinary incontinence subtypes using genome-wide association studies (GWAS).

We conducted a case-control study of women older than 18 with available genetic data and at least one International Classification of Diseases 10 urinary (stress, urge or mixed) incontinence diagnosis between May 2008 and May 2023. Controls had available genetic data with no urinary incontinence diagnosis. Demographic, health, and genomic data were obtained from our institution's electronic medical records and Biobank. Quality control measures applied to the raw data excluded variants with call rate < 95%, with Hardy-Weinberg equilibrium exact p value < 1 × 10^-6, samples with discordant sex, abnormal heterozygote rates, non-European ancestry, or duplicates. The first GWAS run included cases with stress, urge, or mixed incontinence at any point during the study period, whereas the second GWAS run included unique patients with no subtype overlap among the cases.

The first GWAS run had 4270 cases with 5 single-nucleotide polymorphisms (SNPs) significantly associated with mixed and 3 SNPs significantly associated with urgency incontinence (p < 5 × 10^-8). After controlling for overlapping cases, the second GWAS run included 3352 unique patients with 1055 pure stress, 699 pure urgency, and 1598 mixed incontinence. After applying strict filtering, 1 SNP located near the Myoferlin gene was identified on chromosome 10 for mixed, and 1 SNP located near the COX10 divergent transcript gene on chromosome 17 for stress incontinence.

Our study proposes possible new genetic associations in women diagnosed with mixed and stress urinary incontinence that should be validated across other studies.