Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis

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.