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

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; Andrew J Schork; DBDS Genomic Consortium; Thomas Folkmann Hansen

doi:10.1038/s41588-023-01323-z

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

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 SlizMarta 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, Andrew J Schork, DBDS Genomic Consortium, Thomas Folkmann Hansen (Member of study group)

^*Corresponding author for this work

78 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	55
Issue number	3
Pages (from-to)	423-436
Number of pages	14
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-023-01323-z
Publication status	Published - Mar 2023

Keywords

Female
Humans
Endometriosis/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Pain
Comorbidity

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10.1038/s41588-023-01323-z

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Rahmioglu, N., Mortlock, S., Ghiasi, M., Møller, P. L., Stefansdottir, L., Galarneau, G., Turman, C., Danning, R., Law, M. H., Sapkota, Y., Christofidou, P., Skarp, S., Giri, A., Banasik, K., Krassowski, M., Lepamets, M., Marciniak, B., Nõukas, M., Perro, D., ... Hansen, T. F. (2023). The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nature Genetics, 55(3), 423-436. https://doi.org/10.1038/s41588-023-01323-z

Rahmioglu, N, Mortlock, S, Ghiasi, M, Møller, PL, Stefansdottir, L, Galarneau, G, Turman, C, Danning, R, Law, MH, Sapkota, Y, Christofidou, P, Skarp, S, Giri, A, Banasik, K, Krassowski, M, Lepamets, M, Marciniak, B, Nõukas, M, Perro, D, Sliz, E, Sobalska-Kwapis, M, Thorleifsson, G, Topbas-Selcuki, NF, Vitonis, A, Westergaard, D, Arnadottir, R, Burgdorf, KS, Campbell, A, Cheuk, CSK, Clementi, C, Cook, J, De Vivo, I, DiVasta, A, Dorien, O, Donoghue, JF, Edwards, T, Fontanillas, P, Fung, JN, Geirsson, RT, Girling, JE, Harkki, P, Harris, HR, Healey, M, Heikinheimo, O, Holdsworth-Carson, S, Hostettler, IC, Houlden, H, Houshdaran, S, Irwin, JC, Schork, AJ, DBDS Genomic Consortium & Hansen, TF 2023, 'The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions', Nature Genetics, vol. 55, no. 3, pp. 423-436. https://doi.org/10.1038/s41588-023-01323-z

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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.",

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

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Keywords

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