Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.
Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis.
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子宫内膜异位症是一种常见的妇科疾病，伴有盆腔疼痛和生育能力低下。我们对来自澳大利亚和英国的3,194例手术证实的子宫内膜异位症病例和7,060例对照进行了全基因组关联（GWA）研究。多基因预测模型显示，1,364例中重度子宫内膜异位症患者的遗传负荷显著增加。7p15.2（rs 12700667）与“所有”子宫内膜异位症（P = 2.6 × 10−7，OR = 1.22（1.13-1.32））和中重度疾病（P = 1.5 × 10−9（OR = 1.38（1.24-1.53））的关联信号最强。我们在一个独立的美国队列中复制了rs 12700667，该队列包括2,392例自我报告的手术证实的子宫内膜异位症病例和2,271例对照。（P = 1.2 × 10−3，OR = 1.17（1.06-1.28）），在我们的5,586例病例和9,331例对照的联合数据集中，“所有”子宫内膜异位症的全基因组显著P值为1.4 × 10−9（OR = 1.20（1.13-1.27））。SNP rs 12700667位于可能的候选基因NFE 2L 3和HOXA 10上游的基因间区域。
Endometriosis is a common gynaecological disease associated with pelvic pain and sub-fertility. We conducted a genome-wide association (GWA) study in 3,194 surgically confirmed endometriosis cases and 7,060 controls from Australia and the UK. Polygenic predictive modelling showed significantly increased genetic loading among 1,364 cases with moderate-severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for ‘all’ endometriosis (P = 2.6 × 10−7, OR = 1.22 (1.13-1.32)) and for moderate-severe disease (P = 1.5 × 10−9 (OR = 1.38 (1.24-1.53)). We replicated rs12700667 in an independent US cohort of 2,392 self-reported surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10−3, OR = 1.17 (1.06-1.28)), resulting in a genome-wide significant P-value of 1.4 × 10−9 (OR = 1.20 (1.13-1.27)) for ‘all’ endometriosis in our combined datasets of 5,586 cases and 9,331 controls. SNP rs12700667 is located in an inter-genic region upstream of plausible candidate genes NFE2L3 and HOXA10.