Genome-wide association meta-analysis identifies new endometriosis risk loci

Abstract

We conducted a genome-wide association (GWA) meta-analysis of 4,604 endometriosis cases and 9,393 controls of Japanese1 and European2 ancestry. We show that rs12700667 on chromosome 7p15.2, previously found in Europeans, replicates in Japanese (P = 3.6 × 10−3), and confirm association of rs7521902 on 1p36.12 near WNT4. In addition, we establish association of rs13394619 in GREB1 on 2p25.1 and identify a novel locus on 12q22 near VEZT (rs10859871). Excluding European cases with minimal or unknown severity, we identified additional novel loci on 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and produced P < 5 × 10−8 in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the European and Japanese GWA cohorts (P = 8.8 × 10−11), indicating that many weakly associated SNPs represent true endometriosis risk loci and risk prediction and future targeted disease therapy may be transferred across these populations.

Copy number variation analysis reveals additional variants contributing to endometriosis development

“…Our results are in agreement with previous studies that demonstrated an association between 1p36.33 and endometriosis [34][35][36]. This locus contains markers located in or near the WNT4 gene, which plays an important role on the development of the female reproductive tract and steroidogenesis [37,38].…”

Research Priorities for Endometriosis: Recommendations From a Global Consortium of Investigators in Endometriosis

“…29,30 Substantial progress has been made in the discovery of genomic regions contributing to endometriosis risk. New genome-wide association (GWA) studies, 31 replication studies, 32,33 and meta-analyses 30,34 show remarkable consistency in the size and direction of effect for risk variants across studies and across ethnic groups. There are at least 6 genomic regions showing significant association with endometriosis of any disease stage.…”

Recurrent Scar Endometriosis Developing in the episiotomy

“…The genetic factors may increase one's predisposition to endometriosis. It is suggested that genetic factors which are responsible for the etiopathogenesis of the endometriosis are multifactorial and polygenic 10 . The genetic predisposition probably increases the tendency of recurrence of endometriosis lesions with the above mechanisms.…”