The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Journal article

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage III/IV disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN, NGF). We observed significant genetic correlations between endometriosis and 11 pain-conditions including migraine, back, and multisite chronic pain (MCP), as well as inflammatory conditions including asthma and osteoarthritis. Multi-trait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain-conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Authors: Rahmioglu, N; Mortlock, S; Ghiasi, M; Krassowski, M; Perro, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Genetics
• Volume: 55
• Issue: 3
• Pages: 423–436
• Publication date: 2023-03-13
• Acceptance date: 2023-01-27
• DOI: 10.1038/s41588-023-01323-z
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: FFR