title: Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women.
abstract: OBJECTIVE
  Family studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations.
  
  
  METHODS
  PubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including "nocturia," "incontinence," "overactive bladder," "prolapse," and "enuresis." Major genetics, urology, and gynecology conference abstracts were searched from 2005 through 2013. We screened 889 abstracts, and retrieved 78 full texts. In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes. Fixed and random effects metaanalyses were conducted using codominant models of inheritance. We assessed the credibility of pooled associations using the interim Venice criteria.
  
  
  RESULTS
  In pooled analysis, the rs4994 polymorphism of the ADRB3 gene was associated with overactive bladder (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.6; n = 419). The rs1800012 polymorphism of the COL1A1 gene was associated with prolapse (OR, 1.3; 95% CI, 1.0-1.7; n = 838) and stress urinary incontinence (OR, 2.1; 95% CI, 1.4-3.2; n = 190). Other metaanalyses, including those for polymorphisms of COL3A1,LAMC1,MMP1,MMP3, and MMP9 did not show significant effects. Many studies were at high risk of bias from genotyping error or population stratification.
  
  
  CONCLUSIONS
  These metaanalyses provide moderate epidemiological credibility for associations of variation in ADRB3 with overactive bladder, and variation of COL1A1 with prolapse. Clinical testing for any of these polymorphisms cannot be recommended based on current evidence.
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, England, United Kingdom; Department of Urogynecology, Imperial College London, London, England, United Kingdom. Electronic address: r.cartwright@imperial.ac.uk.
authors.forename: Rufus
authors.initials: R
authors.lastname: Cartwright
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, School of Medicine, and Department of Obstetrics and Gynecology, Kaiser Permanente, San Diego, CA.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Kirby
authors.affiliation: Departments of Urology and Public Health, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kari A O
authors.initials: KA
authors.lastname: Tikkinen
authors.affiliation: Department of Urology Research, University of Sheffield, Sheffield, England, United Kingdom.
authors.forename: Altaf
authors.initials: A
authors.lastname: Mangera
authors.affiliation: Department of Urogynecology, King's College London, London, England, United Kingdom.
authors.forename: Gans
authors.initials: G
authors.lastname: Thiagamoorthy
authors.affiliation: Beatson Institute for Cancer Research, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Rajan
authors.affiliation: Department of Urology, University of Tampere, Tampere, Finland.
authors.forename: Jori
authors.initials: J
authors.lastname: Pesonen
authors.affiliation: University College London Medical School, London, England, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Ambrose
authors.affiliation: Clinical Trials Unit, Imperial College London, London, England, United Kingdom.
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez-Maffe
authors.affiliation: Institute for Reproductive and Developmental Biology, Imperial College London, London, England, United Kingdom.
authors.forename: Phillip
authors.initials: P
authors.lastname: Bennett
authors.affiliation: Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, England, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Palmer
authors.affiliation: Department of Genomics of Common Disease and Molecular Genetics and Genomics, Imperial College London, London, England, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walley
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, England, United Kingdom; Institute of Health Sciences and Biocenter Oulu, University of Oulu, Finland.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: Department of Urology Research, University of Sheffield, Sheffield, England, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Chapple
authors.affiliation: Department of Urogynecology, Imperial College London, London, England, United Kingdom.
authors.forename: Vik
authors.initials: V
authors.lastname: Khullar
mesh_terms: D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000235:genetics*; D016017:Odds Ratio; D056887:Pelvic Organ Prolapse / Q000235:genetics*
keywords: genetics; incontinence; lower urinary tract symptoms; overactive bladder; prolapse; systematic review
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