Identification of six loci associated with pelvic organ prolapse using genome-wide association analysis.
Identification of six loci associated with pelvic organ prolapse using genome-wide association analysis.
复制标题
DOI：
10.1097/aog.0b013e318236f4b5
复制
发表时间：
2011-12
影响因子：
7.2
通讯作者：
Norton PA
中科院分区：
文献类型：
--
作者：
Allen-Brady K;Cannon-Albright L;Farnham JM;Teerlink C;Vierhout ME;van Kempen LCL;Kluivers KB;Norton PA
有证据表明环境和遗传因素都会导致盆腔器官脱垂（POP）。我们进行了一项全基因组关联研究，以调查常见的基因变异是否会改变 POP 的风险。我们招募了 1996 年至 2008 年在犹他大学接受过 POP 评估和治疗的女性及其受影响的女性亲属。在 Illumina 550K 平台上对病例进行基因分型。我们对 Illumina 提供的 2,976 个白种人 iControl 作为对照进行了基因匹配。使用两种不同的软件程序对相关受试者的关联测试进行了调整：Efficient Mixed-Model Association eXpedited (EMMAX) 和 Genie。研究结果在一组患有 POP 复发和 POP 家族史的荷兰女性 (n=76) 中得到证实。犹他州的研究样本包括 115 例 POP 治疗病例，大多数病例进行了手术 (n=78) 或重复手术 (n=35)。使用 EMMAX 软件进行关联分析的结果确定了 5 个与 POP 显着相关的单核苷酸多态性 (SNP) (p<1×10−7)。使用 Genie 软件进行独立关联分析，确定了三个相同的 SNP 和一个额外的 SNP。这六个 SNP 位于 4q21 (rs1455311)、8q24 (rs1036819)、9q22 (rs430794)、15q11 (rs8027714)、20p13 (rs1810636) 和 21q22 (rs2236479)。在荷兰队列中的 6 个 SNP 中有 5 个观察到名义上显着的发现 (p<0.05) 或趋向显着性的发现 (p<0.1)。已确定 6 个 SNP 与高风险家族病例中的 POP 显着相关，并为 POP 的遗传贡献提供了证据。
There is evidence that both environmental and genetic factors contribute to pelvic organ prolapse (POP). We conducted a genome-wide association study to investigate whether common genetic variants modify the risk of POP. We recruited women who had been evaluated and treated for POP at the University of Utah from 1996–2008 and their affected female relatives. Cases were genotyped on the Illumina 550K platform. We genetically matched 2,976 Caucasian iControls available from Illumina as controls. Association tests were adjusted for related subjects using two different software programs: Efficient Mixed-Model Association eXpedited (EMMAX) and Genie. Confirmation of findings was performed in a cohort of Dutch women (n=76) with recurrent POP and family history of POP. The Utah study sample included 115 cases treated for POP, in most cases 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 POP (p<1×10−7). 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<0.05) or findings trending towards significance (p<0.1) were observed for five of the six SNPs in the Dutch cohort. Six SNPs have been identified that are significantly associated with POP in high-risk familial cases and provide evidence for a genetic contribution to POP.