title: Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women's Health Initiative.
abstract: Current evidence suggests a multifactorial etiology to pelvic organ prolapse (POP), including genetic predisposition. We conducted a genome-wide association study of POP in African American (AA) and Hispanic (HP) women from the Women's Health Initiative Hormone Therapy study. Cases were defined as any POP (grades 1-3) or moderate/severe POP (grades 2-3), while controls had grade 0 POP. We performed race-specific multiple logistic regression analyses between SNPs imputed to 1000 genomes in relation to POP (grade 0 vs 1-3; grade 0 vs 2-3) adjusting for age at diagnosis, body mass index, parity, and genetic ancestry. There were 1274 controls and 1427 cases of any POP and 317 cases of moderate/severe POP. Although none of the analyses reached genome-wide significance (p<5x10-8), we noted variants in several loci that met p<10-6. In race-specific analysis of grade 0 vs 2-3, intronic SNPs in the CPE gene (rs28573326, OR:2.14; 95% CI 1.62-2.83; p = 1.0x10-7) were associated with POP in AAs, and SNPs in the gene AL132709.5 (rs1950626, OR:2.96; 95% CI 1.96-4.48, p = 2.6x10-7) were associated with POP in HPs. Inverse variance fixed-effect meta-analysis of the race-specific results showed suggestive signals for SNPs in the DPP6 gene (rs11243354, OR:1.36; p = 4.2x10-7) in the grade 0 vs 1-3 analyses and for SNPs around PGBD5 (rs740494, OR:2.17; p = 8.6x10-7) and SHC3 (rs2209875, OR:0.60; p = 9.3x10-7) in the grade 0 vs 2-3 analyses. While we did not identify genome-wide significant findings, we document several SNPs reaching suggestive statistical significance. Further interrogation of POP in larger minority samples is warranted.
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Ayush
authors.initials: A
authors.lastname: Giri
authors.affiliation: Department of Obstetrics and Gynecology, Center for Women's Health Research, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Renee M
authors.initials: RM
authors.lastname: Ward
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, United States of America.|Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.|Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Hartmann
authors.affiliation: Department of Obstetrics and Gynecology and Urology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Park
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Mariaelisa
authors.initials: M
authors.lastname: Graff
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wallace
authors.affiliation: Department of Obstetrics and Gynecology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Gihan
authors.initials: G
authors.lastname: Bareh
authors.affiliation: Department of Public Health Sciences, University of California, Davis, California, United States of America.
authors.forename: Lihong
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Obstetrics and Gynecology, University of Miami, Miami, Florida, United States of America.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: O'Sullivan
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, United States of America.|Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.|Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Edwards
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, United States of America.|Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.|Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Digna R
authors.initials: DR
authors.lastname: Velez Edwards
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics; D060005:Genotyping Techniques; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D056887:Pelvic Organ Prolapse / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016387:Women's Health