Journal
OBSTETRICS AND GYNECOLOGY
Volume 118, Issue 6, Pages 1345-1353Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/AOG.0b013e318236f4b5
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- NICHD NIH HHS [R01 HD041163-03, R01 HD041163-01, R01 HD041163, R01 HD061821, R01 HD061821-02, R01 HD061821-01, R01 HD041163-04, R01 HD003438, R01 HD041163-02, R01 HD061821-03, R01 HD041163-05] Funding Source: Medline
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OBJECTIVE: There is evidence that both environmental and genetic factors contribute to pelvic organ prolapse. We conducted a genome-wide association study to investigate whether common genetic variants modify the risk of pelvic organ prolapse. METHODS: We recruited women who had been evaluated and treated for pelvic organ prolapse at the University of Utah from 1996 to 2008 and their affected female relatives. Those in the case group were genotyped on the Illumina 550K platform. We genetically matched 2,976 white control participants available from Illumina as the control group. Association tests were adjusted for related participants using two different software programs: EMMAX and Genie. Confirmation of findings was performed in a cohort of Dutch women (n=76) with recurrent pelvic organ prolapse and family history of pelvic organ prolapse. RESULTS: The Utah study sample included 115 case group participants treated for pelvic organ prolapse, in most case group participants with surgery (n=78) or repeat surgery (n=35). Results from association analyses using EMMAX software identified five single-nucleotide polymorphisms (SNPs) significantly associated with pelvic organ prolapse (P<1x10(-7)). Independent association analysis with Genie software identified three of the same SNPs and one additional SNP. The six SNPs were located at 4q21 (rs1455311), 8q24 (rs1036819), 9q22 (rs430794), 15q11 (rs8027714), 20p13 (rs1810636), and 21q22 (rs2236479). Nominally significant findings (P<.05) or findings trending toward significance (P<.1) were observed for five of the six SNPs in the Dutch cohort. CONCLUSION: Six SNPs have been identified that are significantly associated with pelvic organ prolapse in high-risk familial case group participants and that provide evidence for a genetic contribution to pelvic organ prolapse. (Obstet Gynecol 2011;118:1345-53) DOI: 10.1097/AOG.0b013e318236f4b5
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