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

DBDS Genomic Consortium; FinnGen Study; FinnGen Endometriosis Taskforce; The Celmatix Research Team; The 23andMe Research Team

doi:10.1038/s41588-023-01323-z

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

DBDS Genomic Consortium
, FinnGen Study
, FinnGen Endometriosis Taskforce
, The Celmatix Research Team
, The 23andMe Research Team

Medicine and Health

University of Oxford
University of Queensland
Michigan State University
Aarhus University
deCODE genetics
Celmatix Inc.
Harvard T.H. Chan School of Public Health
Brigham and Women's Hospital
Queensland Institute of Medical Research
Queensland University of Technology
St. Jude Children's Research Hospital
King's College London
Faculty of Medicine
Vanderbilt School of Medicine
Novo Nordisk Foundation Center for Protein Research
University of Tartu
University of Lodz
University of Oulu
Landspitali - The National University Hospital of Iceland
Copenhagen University Hospital
University of Edinburgh
University of Liverpool
Boston Children's Hospital
Leuven University Center for Metabolic Bone Diseases
Katholieke Universiteit Leuven
University of Melbourne Department of Obstetrics and Gynaecology
23andMe Inc.
University of Otago
University of Helsinki
Fred Hutchinson Cancer Research Center
University College London (UCL)
National Hospital for Neurology and Neurosurgery
Technical University of Munich
University of California San Francisco
Helmholtz Zentrum München German Research Center for Environmental Health
Wellcome Sanger Institute
Oulu University Hospital
College of Health and Life Sciences
RIKEN Center for Integrative Medical Sciences
Institute for Health and Welfare
Research Institute
Tampere University Hospital
Tampere University
Faculty of Medicine
NIHR Biomedical Research Centre at Guy’s and St Thomas’ Foundation Trust
Aristotle University of Thessaloniki
University of Aberdeen
Center for Special Minimally Invasive and Robotic Surgery
University of Glasgow
University of Tartu
Competence Centre on Health Technologies
Medical University of Lublin
Harvard Medical School
MHC Sct. Hans
H. Lundbeck A/S
Translational Genomics Research Institute
Ninewells Hospital and Medical School
National Cerebral and Cardiovascular Center
University of Crete Medical School
Karolinska Institutet
Queensland University of Technology (QUT)
Niigata University Graduate School of Medical and Dental Sciences
The MRC University of Edinburgh Centre for Reproductive Health
Japanese Foundation for Cancer Research
Research and Development
Yale University Medical School
MRC Human Genetics Unit
University of Edinburgh
University of Iceland
Aalborg University
University of Manchester

Research output: Contribution to journal › Article › peer-review

223 Scopus citations

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
Pages (from-to)	423-436
Number of pages	14
Journal	Nature Genetics
Volume	55
Issue number	3
DOIs	https://doi.org/10.1038/s41588-023-01323-z
State	Published - Mar 2023

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@article{5e8dbefc9a8043f1bb4dbeec523abfd0,

title = "The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions",

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.",

author = "\{DBDS Genomic Consortium\} and \{FinnGen Study\} and \{FinnGen Endometriosis Taskforce\} and \{The Celmatix Research Team\} and \{The 23andMe Research Team\} and Nilufer Rahmioglu and Sally Mortlock and Marzieh Ghiasi and M{\o}ller, \{Peter L.\} and Lilja Stefansdottir and Genevi{\`e}ve Galarneau and Constance Turman and Rebecca Danning and Law, \{Matthew H.\} and Yadav Sapkota and Paraskevi Christofidou and Sini Skarp and Ayush Giri and Karina Banasik and Michal Krassowski and Maarja Lepamets and B{\l}a{\.z}ej Marciniak and Margit N{\~o}ukas and Danielle Perro and Eeva Sliz and Marta Sobalska-Kwapis and Gudmar Thorleifsson and Topbas-Selcuki, \{Nura F.\} and Allison Vitonis and David Westergaard and Ragnheidur Arnadottir and Burgdorf, \{Kristoffer S.\} and Archie Campbell and Cheuk, \{Cecilia S.K.\} and Caterina Clementi and James Cook and \{De Vivo\}, Immaculata and Amy DiVasta and O. Dorien and Donoghue, \{Jacqueline F.\} and Todd Edwards and Pierre Fontanillas and Fung, \{Jenny N.\} and Geirsson, \{Reynir T.\} and Girling, \{Jane E.\} and Paivi Harkki and Harris, \{Holly R.\} and Martin Healey and Oskari Heikinheimo and Sarah Holdsworth-Carson and Hostettler, \{Isabel C.\} and Henry Houlden and Sahar Houshdaran and Irwin, \{Juan C.\} and Eleftheria Zeggini",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = mar,

doi = "10.1038/s41588-023-01323-z",

language = "English",

volume = "55",

pages = "423--436",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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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

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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 - Zeggini, Eleftheria

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.

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DO - 10.1038/s41588-023-01323-z

M3 - Article

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AN - SCOPUS:85150092928

SN - 1061-4036

VL - 55

SP - 423

EP - 436

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

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

Abstract

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