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

Publication

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

Journal Paper/Review - Mar 13, 2023

Rahmioglu Nilufer, Mortlock Sally, Ghiasi Marzieh, Møller Peter L, Stefansdottir Lilja, Galarneau Geneviève, Turman Constance, Danning Rebecca, Law Matthew H, Sapkota Yadav, Christofidou Paraskevi, Skarp Sini, Giri Ayush, Banasik Karina, Krassowski Michal, Lepamets Maarja, Marciniak Błażej, Nõukas Margit, Perro Danielle, Sliz Eeva, Sobalska-Kwapis Marta, Thorleifsson Gudmar, Topbas-Selcuki Nura F, Vitonis Allison, Westergaard David, Arnadottir Ragnheidur, Burgdorf Kristoffer S, Campbell Archie, Cheuk Cecilia S K, Clementi Caterina, Cook James P, De Vivo Immaculata, DiVasta Amy, Dorien O, Donoghue Jacqueline F, Edwards Todd L, Fontanillas Pierre, Fung Jenny N, Geirsson Reynir T, Girling Jane E, Harkki Paivi, Harris Holly R, Healey Martin, Heikinheimo Oskari, Holdsworth-Carson Sarah, Hostettler Isabel, Houlden Henry, Houshdaran Sahar, Irwin Juan C, Jarvelin Marjo-Riitta, Kamatani Yoichiro, Kennedy Stephen H, Kepka Ewa, Kettunen Johannes, Kubo Michiaki, Kulig Bartosz, Kurra Venla, Laivuori Hannele, Laufer Marc R, Lindgren Cecilia M, MacGregor Stuart, Mangino Massimo, Martin Nicholas G, Matalliotaki Charoula, Matalliotakis Michail, Murray Alison D, Ndungu Anne, Nezhat Camran, Olsen Catherine M, Opoku-Anane Jessica, Padmanabhan Sandosh, Paranjpe Manish, Peters Maire, Polak Grzegorz, Porteous David J, Rabban Joseph, Rexrode KathyM, Romanowicz Hanna, Saare Merli, Saavalainen Liisu, Schork Andrew J, Sen Sushmita, Shafrir Amy L, Siewierska-Górska Anna, Słomka Marcin, Smith Blair H, Smolarz Beata, Szaflik Tomasz, Szyłło Krzysztof, Takahashi Atsushi, Terry Kathryn L, Tomassetti Carla, Treloar Susan A, Vanhie Arne, Vincent Katy, Vo Kim C, Werring David J, Zeggini Eleftheria, Zervou Maria I, DBDS Genomic Consortium, FinnGen Study, FinnGen Endometriosis Taskforce, Celmatix Research Team, 23andMe Research Team, Adachi Sosuke, Buring Julie E, Ridker Paul M, D'Hooghe Thomas, Goulielmos George N, Hapangama Dharani K, Hayward Caroline, Horne Andrew W, Low Siew-Kee, Martikainen Hannu, Chasman Daniel I, Rogers Peter A W, Saunders Philippa T, Sirota Marina, Spector Timothy D, Strapagiel Dominik, Tung Joyce Y, Whiteman David C, Giudice Linda C, Velez Edwards Digna R, Uimari Outi, Kraft Peter, Salumets Andres, Nyholt Dale R, Mägi Reedik, Stefansson Kari, Becker Christian M, Yurttas-Beim Piraye, Steinthorsdottir Valgerdur, Nyegaard Mette, Missmer Stacey A, Montgomery Grant W, Morris Andrew P, Zondervan Krina T

Citation

Rahmioglu N, Mortlock S, Ghiasi M, Møller P, Stefansdottir L, Galarneau G, Turman C, Danning R, Law M, 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 N, Vitonis A, Westergaard D, Arnadottir R, Burgdorf K, Campbell A, Cheuk C, Clementi C, Cook J, De Vivo I, DiVasta A, Dorien O, Donoghue J, Edwards T, Fontanillas P, Fung J, Geirsson R, Girling J, Harkki P, Harris H, Healey M, Heikinheimo O, Holdsworth-Carson S, Hostettler I, Houlden H, Houshdaran S, Irwin J, Jarvelin M, Kamatani Y, Kennedy S, Kepka E, Kettunen J, Kubo M, Kulig B, Kurra V, Laivuori H, Laufer M, Lindgren C, MacGregor S, Mangino M, Martin N, Matalliotaki C, Matalliotakis M, Murray A, Ndungu A, Nezhat C, Olsen C, Opoku-Anane J, Padmanabhan S, Paranjpe M, Peters M, Polak G, Porteous D, Rabban J, Rexrode K, Romanowicz H, Saare M, Saavalainen L, Schork A, Sen S, Shafrir A, Siewierska-Górska A, Słomka M, Smith B, Smolarz B, Szaflik T, Szyłło K, Takahashi A, Terry K, Tomassetti C, Treloar S, Vanhie A, Vincent K, Vo K, Werring D, Zeggini E, Zervou M, DBDS Genomic Consortium, FinnGen Study, FinnGen Endometriosis Taskforce, Celmatix Research Team, 23andMe Research Team, Adachi S, Buring J, Ridker P, D'Hooghe T, Goulielmos G, Hapangama D, Hayward C, Horne A, Low S, Martikainen H, Chasman D, Rogers P, Saunders P, Sirota M, Spector T, Strapagiel D, Tung J, Whiteman D, Giudice L, Velez Edwards D, Uimari O, Kraft P, Salumets A, Nyholt D, Mägi R, Stefansson K, Becker C, Yurttas-Beim P, Steinthorsdottir V, Nyegaard M, Missmer S, Montgomery G, Morris A, Zondervan K. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet 2023; 55:423-436.

Type

Journal Paper/Review (English)

Journal

Nat Genet 2023; 55

Publication Date

Mar 13, 2023

Issn Electronic

1546-1718

Pages

423-436

Brief description/objective

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.