abstract

• To identify genetic variants associated with urgency urinary incontinence (UUI) in post-menopausal women.A two-stage genome wide association analysis was conducted to identify variants associated with UUI. The Women's Health Initiative-Genomics & Randomized Trials Network (GARNET) sub-study with 4,894 genotyped post-reproductive white women was randomly split into independent discovery and replication cohorts. Genome-wide imputation was performed using IMPUTE2 with the 1000-Genomes-ALL-Phase-I integrated variant set as a reference. Controls reported no UUI at enrollment or follow-up; cases reported monthly or greater UUI and leaked sufficiently to wet/soak underpants/clothes. Logistic regression models were used to predict UUI case versus control status based on genotype, assuming additive inheritance. Age, obesity, diabetes and depression were included in the models as covariates.Following quality control, 975,508 single nucleotide polymorphisms (SNPs) in 2,241 cases (discovery=1,102, replication=1,133) and 776 controls (discovery=405, replication=371) remained. Genotype imputation resulted in 9,077,347 SNPs and insertions/deletions with minor allele frequency >0.01 available for analysis. Meta-analysis of the discovery and replication samples identified six loci on chromosomes 5, 10, 11, 12 & 18 associated with UUI at p<10(-6). Three of the loci were within genes, the zinc finger protein 521 (ZFP521) gene on chromosome 18q11, the ADAMTS16 gene on chromosome 5p15, and the CIT gene on chromosome 12q24. The other three loci were intergenic.Although environmental factors also likely contribute, this first exploratory Genome-Wide Associated Study (GWAS) for UUI suggests that genetic variants in the ZFP521, CIT, and ADAMTS16 genes might account for some of the observed heritability of the condition.Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

authors

• Richter, Holly E
• Whitehead, Nedra
• Arya, Lily
• Ridgeway, Beri
• Allen-Brady, Kristina
• Norton, Peggy
• Sung, Vivian
• Shepherd, Jonathan P
• Komesu, Yuko
• Gaddis, Nathan C
• Fraser, Matthew
• Tan-Kim, Jasmine
• Meikle, Susan
• Page, Grier P
• Pelvic Floor Disorders Network

publication date

• December 2014

Digital Object Identifier (DOI)

• https://doi.org/10.1016/j.juro.2014.12.023

PubMed ID

• 25524241

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