Journal article
Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women's Health Initiative
PloS one, Vol.10(11), pp.e0141647-e0141647
2015
DOI: 10.1371/journal.pone.0141647
PMCID: PMC4636147
PMID: 26545240
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.
Details
- Title: Subtitle
- Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women's Health Initiative
- Creators
- Ayush Giri - Vanderbilt UniversityJennifer M Wu - University of North Carolina at Chapel HillRenee M Ward - Vanderbilt University Medical CenterKatherine E Hartmann - Vanderbilt UniversityAmy J Park - Georgetown UniversityKari E North - University of North Carolina at Chapel HillMariaelisa Graff - University of North Carolina at Chapel HillRobert B Wallace - University of IowaGihan Bareh - Loma Linda UniversityLihong Qi - University of California, DavisMary J O'Sullivan - University of MiamiAlexander P Reiner - University of WashingtonTodd L Edwards - Vanderbilt UniversityDigna R Velez Edwards - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.10(11), pp.e0141647-e0141647
- DOI
- 10.1371/journal.pone.0141647
- PMID
- 26545240
- PMCID
- PMC4636147
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Grant note
- UL1 RR024975 / NCRR NIH HHS P30 CA015704 / NCI NIH HHS K23 HD068404 / NICHD NIH HHS N01WH32122 / WHI NIH HHS N02-HL-64278 / NHLBI NIH HHS 5K12HD04383-11 / NICHD NIH HHS N01WH32100-2 / WHI NIH HHS N01WH32118-32119 / WHI NIH HHS N01WH32115 / WHI NIH HHS N01WH32108-9 / WHI NIH HHS N01WH24152 / WHI NIH HHS N02HL64278 / NHLBI NIH HHS N01WH42129-32 / WHI NIH HHS N01WH42107-26 / WHI NIH HHS K23HD068404 / NICHD NIH HHS N01WH44221 / WHI NIH HHS N01WH22110 / WHI NIH HHS N01WH32111-13 / WHI NIH HHS 5KL2RR024975 / NCRR NIH HHS N01WH32105-6 / WHI NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363667602771
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