Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial.
Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ance...
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Public Library of Science (PLoS)
2017-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0178839 |
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| author | Ayush Giri Katherine E Hartmann Melinda C Aldrich Renee M Ward Jennifer M Wu Jennifer M Wu Amy J Park Mariaelisa Graff Lihong Qi Rami Nassir Robert B Wallace Mary J O'Sullivan Kari E North Digna R Velez Edwards Todd L Edwards |
| author_facet | Ayush Giri Katherine E Hartmann Melinda C Aldrich Renee M Ward Jennifer M Wu Jennifer M Wu Amy J Park Mariaelisa Graff Lihong Qi Rami Nassir Robert B Wallace Mary J O'Sullivan Kari E North Digna R Velez Edwards Todd L Edwards |
| author_sort | Ayush Giri |
| collection | DOAJ |
| description | Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women's Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk. |
| format | Article |
| id | doaj-art-74e2cd8a3e2d4bf083cd80acc9b5a488 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
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| spelling | doaj-art-74e2cd8a3e2d4bf083cd80acc9b5a4882025-08-20T03:24:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017883910.1371/journal.pone.0178839Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial.Ayush GiriKatherine E HartmannMelinda C AldrichRenee M WardJennifer M WuJennifer M WuAmy J ParkMariaelisa GraffLihong QiRami NassirRobert B WallaceMary J O'SullivanKari E NorthDigna R Velez EdwardsTodd L EdwardsEvidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women's Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.https://doi.org/10.1371/journal.pone.0178839 |
| spellingShingle | Ayush Giri Katherine E Hartmann Melinda C Aldrich Renee M Ward Jennifer M Wu Jennifer M Wu Amy J Park Mariaelisa Graff Lihong Qi Rami Nassir Robert B Wallace Mary J O'Sullivan Kari E North Digna R Velez Edwards Todd L Edwards Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. PLoS ONE |
| title | Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. |
| title_full | Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. |
| title_fullStr | Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. |
| title_full_unstemmed | Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. |
| title_short | Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial. |
| title_sort | admixture mapping of pelvic organ prolapse in african americans from the women s health initiative hormone therapy trial |
| url | https://doi.org/10.1371/journal.pone.0178839 |
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