Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Queensland, Australia.
Nat Genet. 2011 Jan;43(1):51-4. doi: 10.1038/ng.731. Epub 2010 Dec 12.
Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10⁻⁷, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10⁻⁹, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10⁻³, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10⁻⁹ (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.
子宫内膜异位症是一种常见的妇科疾病，与盆腔疼痛和不孕有关。我们在澳大利亚和英国的 3194 名经手术证实患有子宫内膜异位症（病例）和 7060 名对照者中进行了全基因组关联研究（GWAS）。多基因预测模型显示，1364 名中至重度子宫内膜异位症患者的遗传负荷显著增加。最强的关联信号位于 7p15.2（rs12700667），用于“所有”子宫内膜异位症（P=2.6×10⁻⁷，比值比（OR）=1.22，95%CI 1.13-1.32）和中至重度疾病（P=1.5×10⁻⁹，OR=1.38，95%CI 1.24-1.53）。我们在来自美国的 2392 名自我报告、经手术证实的子宫内膜异位症病例和 2271 名对照者的独立队列中复制了 rs12700667（P=1.2×10⁻³，OR=1.17，95%CI 1.06-1.28），导致我们在 5586 例病例和 9331 例对照者的综合数据集的全基因组显著 P 值为 1.4×10⁻⁹（OR=1.20，95%CI 1.13-1.27），用于“所有”子宫内膜异位症。rs12700667位于合理候选基因 NFE2L3 和 HOXA10 上游的基因间区域。
