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

Nilufer Rahmioglu; Sally Mortlock; Marzieh Ghiasi; Peter L. Moller; Lilja Stefansdottir; Genevieve Galarneau; Constance Turman; Rebecca Danning; Matthew H. Law; Yadav Sapkota; Paraskevi Christofidou; Sini Skarp; Ayush Giri; Karina Banasik; Michal Krassowski; Maarja Lepamets; Blazej Marciniak; Margit Noukas; 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; 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-Gorska; Marcin Slomka; Blair H. Smith; Beata Smolarz; Tomasz Szaflik; Krzysztof Szyllo; Atsushi Takahashi; Kathryn L. Terry; Carla Tomassetti; Susan A. Treloar; Arne Vanhie; Katy Vincent; Kim C. Vo; David J. Werring; Eleftheria Zeggini; Maria Zervou; Kari Stefansson; Mette Nyegaard; Outi Uimari; Piraye Yurttas-Beim; Joyce Y. Tung; 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 Chasman; Peter A. W. Rogers; Philippa T. Saunders; Marina Sirota; Tim Spector; Dominik Strapagiel; David C. Whiteman; Linda C. Giudice; Digna R. Velez-Edwards; Peter Kraft; Andres Salumets; Dale R. Nyholt; Reedik Magi; Christian M. Becker; Valgerdur Steinthorsdottir; Stacey A. Missmer; Grant W. Montgomery; Andrew P. Morris; Krina T. Zondervan; DBDS Genomic Consortium

doi:10.1038/s41588-023-01323-z

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

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

Nilufer Rahmioglu, Sally Mortlock, Marzieh Ghiasi, Peter L. Moller, Lilja Stefansdottir, Genevieve Galarneau, Constance Turman, Rebecca Danning, Matthew H. Law, Yadav Sapkota, …

Nature genetics, Vol.55(3), pp.423-436

01/03/2023

DOI: https://doi.org/10.1038/s41588-023-01323-z

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https://hdl.handle.net/10523/18923

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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. Meta-analyses of genome-wide association studies for endometriosis identify 49 distinct association signals. Fine-mapping of causal variants explores functional effects across various tissues. Genetic correlations between endometriosis and other pain conditions are also highlighted.

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Record Identifier: 9926495660401891
Title: The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
Creators: Nilufer Rahmioglu
Sally Mortlock
Marzieh Ghiasi
Peter L. Moller
Lilja Stefansdottir
Genevieve Galarneau
Constance Turman
Rebecca Danning
Matthew H. Law
Yadav Sapkota
Paraskevi Christofidou
Sini Skarp
Ayush Giri
Karina Banasik
Michal Krassowski
Maarja Lepamets
Blazej Marciniak
Margit Noukas
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
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-Gorska
Marcin Slomka
Blair H. Smith
Beata Smolarz
Tomasz Szaflik
Krzysztof Szyllo
Atsushi Takahashi
Kathryn L. Terry
Carla Tomassetti
Susan A. Treloar
Arne Vanhie
Katy Vincent
Kim C. Vo
David J. Werring
Eleftheria Zeggini
Maria Zervou
Kari Stefansson
Mette Nyegaard
Outi Uimari
Piraye Yurttas-Beim
Joyce Y. Tung
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 Chasman
Peter A. W. Rogers
Philippa T. Saunders
Marina Sirota
Tim Spector
Dominik Strapagiel
David C. Whiteman
Linda C. Giudice
Digna R. Velez-Edwards
Peter Kraft
Andres Salumets
Dale R. Nyholt
Reedik Magi
Christian M. Becker
Valgerdur Steinthorsdottir
Stacey A. Missmer
Grant W. Montgomery
Andrew P. Morris
Krina T. Zondervan
DBDS Genomic Consortium
Publication Details: Nature genetics, Vol.55(3), pp.423-436
Academic Unit: Anatomy
Publisher: Nature Portfolio
Grant note: Cerylid Biosciences (Melbourne) Australian Government Medical Research Future Fund Research Grant; Medical Research Future Fund (MRFF) Chronic Disease Research Foundation (CDRF) NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA MRC University Unit Programme Grant; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NIH NICHD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Novo Nordisk Foundation; Novocure Limited MSCA-RISE-2020 project TRENDO NNF14CC0001 / Medical Research Council UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Li Ka Shing Foundation NICHD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Versus Arthritis Academy of Finland; Research Council of Finland Australian National Health and Medical Research Council; National Health and Medical Research Council (NHMRC) of Australia Polish POIG grant HR03006 / Scottish Funding Council EU; European Union (EU) National Institute for Health Research (NIHR); National Institutes of Health Research (NIHR) Sigrid Juselius Foundation Wellbeing of Women UK; Wellbeing of Women (WoW) European Regional Development Fund; European Union (EU) 1P50HD104224-01; INV-024200 / King's College London NIHR Oxford Biomedical Research Centre, Oxford Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC); Australian Government; Department of Industry, Innovation and Science; Cooperative Research Centres (CRC) Programme Estonian Research Council CZD/16/6 / Chief Scientist Office of the Scottish Government Health Directorates; Chief Scientist Office - Scotland Enter-prise Estonia Nezhat Family Foundation NNF14CC0001; FT0991022; MRF1199785; 21754; PRG1911; PRG1076; EU952516; EU48695; 101008193; 01.01.02-10-005/08; NNF17OC0027594; NNF18SA0034956; R01HD089511; R21 HD096358; R01 HD094842; 297338; 307247 / National Health and Medical Research Council (NHMRC) of Australia Wellcome Trust Case-Control Consortium; Wellcome Trust National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Eunice Kennedy Shriver National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Wellbeing of Women; Wellbeing of Women (WoW) Gates Foundation; Bill & Melinda Gates Foundation European Commission; European Union (EU); European Commission Joint Research Centre APP1073898; APP1063061; NNF17OC0026062 / Wellcome Trust J. Willard and Alice S. Marriott Foundation ARC; Australian Research Council INV-024200 / Bill and Melinda Gates Foundation; Bill & Melinda Gates Foundation NNF17OC0027594; NNF21OC0071050 / European Union; European Union (EU) NHMRC; National Health and Medical Research Council (NHMRC) of Australia
Date published ; e-published: 01/03/2023
Language: English
Resource Type ; Subtype: Journal article