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

Disease areas:

reproductive and urinary health

Last updated:: 19 November 2025

Author(s):: Nilufer Rahmioglu, Sally Mortlock, Marzieh Ghiasi, Peter L. Møller, Lilja Stefansdottir, Geneviève Galarneau, Constance Turman, Rebecca Danning, Matthew H. Law, Yadav Sapkota, Paraskevi Christofidou, Sini Skarp, Ayush Giri, Karina Banasik, Michal Krassowski, Maarja Lepamets, Błażej Marciniak, Margit Nõukas, Danielle Perro, Eeva Sliz, Marta Sobalska-Kwapis, Gudmar Thorleifsson, Nura F. Topbas-Selcuki, Allison Vitonis, David Westergaard, Ragnheidur Arnadottir, Kristoffer S. Burgdorf, Archie Campbell, Cecilia S. K. Cheuk, Caterina Clementi, James Cook, Immaculata De Vivo, Amy DiVasta, O. Dorien, Jacqueline F. Donoghue, Todd Edwards, Pierre Fontanillas, Jenny N. Fung, Reynir T. Geirsson, Jane E. Girling, Paivi Harkki, Holly R. Harris, Martin Healey, Oskari Heikinheimo, Sarah Holdsworth-Carson, Isabel C. Hostettler, Henry Houlden, Sahar Houshdaran, Juan C. Irwin, Marjo-Riitta Jarvelin, Yoichiro Kamatani, Stephen H. Kennedy, Ewa Kepka, Johannes Kettunen, Michiaki Kubo, Bartosz Kulig, Venla Kurra, Hannele Laivuori, Marc R. Laufer, Cecilia M. Lindgren, Stuart MacGregor, Massimo Mangino, Nicholas G. Martin, Charoula Matalliotaki, Michail Matalliotakis, Alison D. Murray, Anne Ndungu, Camran Nezhat, Catherine M. Olsen, Jessica Opoku-Anane, Sandosh Padmanabhan, Manish Paranjpe, Maire Peters, Grzegorz Polak, David J. Porteous, Joseph Rabban, Kathyrn M. Rexrode, Hanna Romanowicz, Merli Saare, Liisu Saavalainen, Andrew J. Schork, Sushmita Sen, Amy L. Shafrir, Anna Siewierska-Górska, Marcin Słomka, Blair H. Smith, Beata Smolarz, Tomasz Szaflik, Krzysztof Szyłło, Atsushi Takahashi, Kathryn L. Terry, Carla Tomassetti, Susan A. Treloar, Arne Vanhie, Katy Vincent, Kim C. Vo, David J. Werring, Eleftheria Zeggini, Maria I. Zervou, Sosuke Adachi, Julie E. Buring, Paul M. Ridker, Thomas D'Hooghe, George N. Goulielmos, Dharani K. Hapangama, Caroline Hayward, Andrew W. Horne, Siew-Kee Low, Hannu Martikainen, Daniel I. Chasman, Peter A. W. Rogers, Philippa T. Saunders, Marina Sirota, Tim Spector, Dominik Strapagiel, Joyce Y. Tung, David C. Whiteman, Linda C. Giudice, Digna R. Velez-Edwards, Outi Uimari, Peter Kraft, Andres Salumets, Dale R. Nyholt, Reedik Mägi, Kari Stefansson, Christian M. Becker, Piraye Yurttas-Beim, Valgerdur Steinthorsdottir, Mette Nyegaard, Stacey A. Missmer, Grant W. Montgomery, Andrew P. Morris, Krina T. Zondervan
Publish date:: 13 March 2023
Journal:: Nature Genetics
PubMed ID:: 36914876
DOI:: 10.1038/s41588-023-01323-z

Abstract

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.