The Association between Endometriosis and Immunological diseases

Abstract

The evidence for a greater prevalence of immunological-diseases among endometriosis patients has varied in robustness and been subject to selection bias. We investigated the phenotypic and genetic association between endometriosis and 31 immunological-diseases in the UK Biobank (8,223 endometriosis, 64,620 immunological-disease cases). In cross-sectional and retrospective cohort analyses, endometriosis patients were at significantly increased (30-80%) risk of classical- autoimmune (rheumatoid arthritis, multiple sclerosis, coeliac disease), autoinflammatory (osteoarthritis) and mixed-pattern (psoriasis) diseases. Osteoarthritis (genetic-correlation (rg)=0.28, P=3.25x10-15), rheumatoid arthritis (rg=0.27, P=1.54x10-5) and multiple sclerosis (rg=0.09, P=4.00x10-3) were significantly genetically correlated with endometriosis. Mendelian randomisation analysis suggested a causal association between endometriosis and rheumatoid arthritis (OR=1.16, 95%CI=1.02-1.33). Expression QTL analyses highlighted effector genes enriched for seven pathways across all four conditions, with three genetic loci shared between endometriosis and osteoarthritis and one with rheumatoid arthritis. Although the increased risk of immunological-diseases among endometriosis patients is modest, their shared genetic basis opens-up opportunities for new treatments.