TY - JOUR
T1 - The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
AU - DBDS Genomic Consortium
AU - FinnGen
AU - FinnGen Endometriosis Taskforce
AU - The Celmatix Research Team
AU - The 23andMe Research Team
AU - Morris, Andrew P.
AU - et al,
PY - 2023/3/13
Y1 - 2023/3/13
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-023-01323-z
DO - 10.1038/s41588-023-01323-z
M3 - Article
SN - 1061-4036
VL - 55
SP - 423
EP - 436
JO - Nature Genetics
JF - Nature Genetics
ER -
