title: Genetic contributions to urgency urinary incontinence in women.
abstract: OBJECTIVE
  We identify genetic variants associated with urgency urinary incontinence in postmenopausal women.
  
  
  METHODS
  A 2-stage genome-wide association analysis was conducted to identify variants associated with urgency urinary incontinence. The WHI GARNET substudy 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 urgency urinary incontinence at enrollment or followup. Cases reported monthly or greater urgency urinary incontinence and leaked sufficiently to wet/soak underpants/clothes. Logistic regression models were used to predict urgency urinary incontinence case vs control status based on genotype, assuming additive inheritance. Age, obesity, diabetes and depression were included in the models as covariates.
  
  
  RESULTS
  Following quality control, 975,508 single nucleotide polymorphisms 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 single nucleotide polymorphisms and insertions/deletions with minor allele frequency greater than 0.01 available for analysis. Meta-analysis of the discovery and replication samples identified 6 loci on chromosomes 5, 10, 11, 12 and 18 associated with urgency urinary incontinence at p <10(-6). Of the loci 3 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 3 loci were intergenic.
  
  
  CONCLUSIONS
  Although environmental factors also likely contribute, this first exploratory genome-wide association study for urgency urinary incontinence suggests that genetic variants in the ZFP521, CIT and ADAMTS16 genes might account for some of the observed heritability of the condition.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: hrichter@uabmc.edu.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Richter
authors.affiliation: Research Triangle International, Research Triangle Park, North Carolina.
authors.forename: Nedra
authors.initials: N
authors.lastname: Whitehead
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Lily
authors.initials: L
authors.lastname: Arya
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Beri
authors.initials: B
authors.lastname: Ridgeway
authors.affiliation: University of Utah, Salt Lake City, Utah.
authors.forename: Kristina
authors.initials: K
authors.lastname: Allen-Brady
authors.affiliation: University of Utah, Salt Lake City, Utah.
authors.forename: Peggy
authors.initials: P
authors.lastname: Norton
authors.affiliation: Warren Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Vivian
authors.initials: V
authors.lastname: Sung
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Shepherd
authors.affiliation: University of New Mexico, Albuquerque, New Mexico.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Komesu
authors.affiliation: Research Triangle International, Research Triangle Park, North Carolina.
authors.forename: Nathan
authors.initials: N
authors.lastname: Gaddis
authors.affiliation: Duke University, Durham, North Carolina.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Fraser
authors.affiliation: Kaiser Permanente, San Diego, California.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Tan-Kim
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Meikle
authors.affiliation: Research Triangle International, Research Triangle Park, North Carolina.
authors.forename: Grier P
authors.initials: GP
authors.lastname: Page
mesh_terms: D000368:Aged; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D053202:Urinary Incontinence, Urge / Q000235:genetics*
keywords: genome-wide association study; overactive; urge; urinary bladder; urinary incontinence