TY - JOUR
T1 - The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
AU - DBDS Genomic Consortium
AU - FinnGen Study
AU - FinnGen Endometriosis Taskforce
AU - The Celmatix Research Team
AU - The 23andMe Research Team
AU - Rahmioglu, Nilufer
AU - Mortlock, Sally
AU - Ghiasi, Marzieh
AU - Møller, Peter L.
AU - Stefansdottir, Lilja
AU - Galarneau, Geneviève
AU - Turman, Constance
AU - Danning, Rebecca
AU - Law, Matthew H.
AU - Sapkota, Yadav
AU - Christofidou, Paraskevi
AU - Skarp, Sini
AU - Giri, Ayush
AU - Banasik, Karina
AU - Krassowski, Michal
AU - Lepamets, Maarja
AU - Marciniak, Błażej
AU - Nõukas, Margit
AU - Perro, Danielle
AU - Sliz, Eeva
AU - Sobalska-Kwapis, Marta
AU - Thorleifsson, Gudmar
AU - Topbas-Selcuki, Nura F.
AU - Vitonis, Allison
AU - Westergaard, David
AU - Arnadottir, Ragnheidur
AU - Burgdorf, Kristoffer S.
AU - Campbell, Archie
AU - Cheuk, Cecilia S.K.
AU - Clementi, Caterina
AU - Cook, James
AU - De Vivo, Immaculata
AU - DiVasta, Amy
AU - Dorien, O.
AU - Donoghue, Jacqueline F.
AU - Edwards, Todd
AU - Fontanillas, Pierre
AU - Fung, Jenny N.
AU - Geirsson, Reynir T.
AU - Girling, Jane E.
AU - Harkki, Paivi
AU - Harris, Holly R.
AU - Healey, Martin
AU - Heikinheimo, Oskari
AU - Holdsworth-Carson, Sarah
AU - Hostettler, Isabel C.
AU - Houlden, Henry
AU - Houshdaran, Sahar
AU - Irwin, Juan C.
AU - Galarneau, Geneviève
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/3
Y1 - 2023/3
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 3/4 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 and 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. Multitrait 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 3/4 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 and 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. Multitrait 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.
UR - http://www.scopus.com/inward/record.url?scp=85150092928&partnerID=8YFLogxK
U2 - 10.1038/s41588-023-01323-z
DO - 10.1038/s41588-023-01323-z
M3 - Article
C2 - 36914876
AN - SCOPUS:85150092928
SN - 1061-4036
VL - 55
SP - 423
EP - 436
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -