Discovery of novel loci for endometriosis in genome-wide association analysis of 63 K cases and 700 K controls

Discovery of novel loci for endometriosis in genome-wide association analysis of 63K cases and 700K controls Study question (maximum 25 words):What common genetic variants and corresponding functional mechanisms, underlie endometriosis, and its surgical sub-types (ASRM-stages), clinical sub-types (Infertile-endometriosis) and symptombased sub-types (Severe pelvic-pain with endometriosis)? Summary answer (maximum 25 words):With the largest sample size to date for endometriosis genome-wide-association-study (GWAS) metaanalysis, we expect to identify many novel susceptibility loci for this debilitating condition. What is known already (maximum 100 words):Endometriosis has an estimated heritability of ~ 50%, with ~26% estimated to be related to common genetic variation.To date, meta-analysis of endometriosis GWAS (17K cases and 191K controls) have robustly identified 19 variants explaining 5.2% of disease variance.Previous GWAS analyses also highlighted that the signals for most of the genome-wide significant loci are driven by ASRM stage III/IV disease, highlighting the need for further phenotype-stratified analyses. Study design, size, duration (maximum 75 words):IEGC consists of 25-centres, in total contributing 63K endometriosis cases, 7800 stage III/IV, and 700K controls to the GWAS meta-analysis.Some of these are population-based cohorts such as the UK Biobank, and also clinical-investigations such as ENDOX, which is a prospective study recruiting women undergoing laparoscopy, that has dense clinical phenotype data.Some of the centres have expression and eQTL datasets for endometrium, fat and ectopic-disease-tissue, allowing for evaluation of functional mechanisms of the identified genetic variants.