TY - JOUR
T1 - Genetic determinants of pelvic organ prolapse among African American and Hispanic women in the Women's Health Initiative
AU - Giri, Ayush
AU - Wu, Jennifer M.
AU - Ward, Renee M.
AU - Hartmann, Katherine E.
AU - Park, Amy J.
AU - North, Kari E.
AU - Graff, Mariaelisa
AU - Wallace, Robert B.
AU - Bareh, Gihan
AU - Qi, Lihong
AU - O'Sullivan, Mary J.
AU - Reiner, Alexander P.
AU - Edwards, Todd L.
AU - Edwards, Digna R.Velez
N1 - Publisher Copyright:
© 2015 Giri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/11/6
Y1 - 2015/11/6
N2 - 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<5×10-8), 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 = 1.0×10-7) were associated with POP in AAs, and SNPs in the gene AL132709.5 (rs1950626, OR:2.96; 95% CI 1.96-4.48, p = 2.6×10-7) 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 = 4.2×10-7) in the grade 0 vs 1-3 analyses and for SNPs around PGBD5 (rs740494, OR:2.17; p = 8.6×10-7) and SHC3 (rs2209875, OR:0.60; p = 9.3×10-7) 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.
AB - 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<5×10-8), 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 = 1.0×10-7) were associated with POP in AAs, and SNPs in the gene AL132709.5 (rs1950626, OR:2.96; 95% CI 1.96-4.48, p = 2.6×10-7) 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 = 4.2×10-7) in the grade 0 vs 1-3 analyses and for SNPs around PGBD5 (rs740494, OR:2.17; p = 8.6×10-7) and SHC3 (rs2209875, OR:0.60; p = 9.3×10-7) 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.
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U2 - 10.1371/journal.pone.0141647
DO - 10.1371/journal.pone.0141647
M3 - Article
C2 - 26545240
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e0141647
ER -