ArticleResearch square2025
Expanding the genetic landscape of endometriosis: Integrative -omics analyses implicate key genes and pathways in a multi-ancestry study of over one million women.
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39 authors.
Lindsay A GuarePathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.ORCID 0000-0001-6988-5319
Jagyashila DasPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Lannawill CaruthPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Ananya RajagopalanGenomics and Computational Biology, University of Pennsylvania, Philadelphia, PA, United States.
Alexis T AkereleDivision of Quantitative Science, Department of Obstetrics and Gynecology, Department of Microbiology, Immunology, and Physiology, Vanderbilt University Medical Center, and Meharry Medical College, Nashville, TN, United States.
Ben M BrumptonHUNT Center for Molecular and Clinical Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway.ORCID 0000-0002-3058-1059
Tzu-Ting ChenCenter for Neuropsychiatric Research, National Health Research Institutes, Maoli County, Taiwan.
Leah KottyanCincinnati Children's Hospital Medical Center, Cincinatti, OH, United States.
Yen-Feng LinCenter for Neuropsychiatric Research, National Health Research Institutes, Maoli County, Taiwan.ORCID 0000-0003-3017-6026
Elisa MorenoHUNT Center for Molecular and Clinical Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway.
Ashley J MulfordEndeavor Health, Evanston, IL, United States.
Marija Simona DombrovskaLatvian Biomedical Research and Study Centre, Riga, Latvia.
Yuan LuoFeinberg School of Medicine, Northwestern University, Chicago, IL, United States.ORCID 0000-0003-0195-7456
Vita RoviteLatvian Biomedical Research and Study Centre, Riga, Latvia.
Alan R SandersEndeavor Health, Evanston, IL, United States.ORCID 0000-0001-6629-4011
Craig TeerlinkVA Informatics and Computing Infrastructure, VA Salt Lake City Healthcare System, Salte Lake City, UT, United States.
Danielle CandelieriVA Informatics and Computing Infrastructure, VA Salt Lake City Healthcare System, Salte Lake City, UT, United States.
Noemie ElhadadBiomedical Informatics, Columbia University, New York City, NY, United States.
Andrew HillColorado for Precision Medicine, Aurora, CO, United States.
Gail P JarvikDivision of Medical Genetics, University of Washington, Seattle, WA, United States.
James JaworskiDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Julie LynchVA Informatics and Computing Infrastructure, VA Salt Lake City Healthcare System, Salte Lake City, UT, United States.ORCID 0000-0003-0108-2127
Shinichi NambaGenome Informatics, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-7486-3146
Yukinori OkadaGenome Informatics, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-0311-8472
Yue ShiBroad Institute, Cambridge, MA, United States.
Yuya ShiraiStatistical Genetics, Osaka University, Suita, Osaka, Japan.ORCID 0000-0002-0518-9020
Jonathan ShorttColorado for Precision Medicine, Aurora, CO, United States.ORCID 0000-0002-7980-5420
Wei-Qi WeiBiomedical Informatics, Vanderbilt University, Nashville, TN, United States.ORCID 0000-0003-4985-056X
Chunhua WengBiomedical Informatics, Columbia University, New York City, NY, United States.
Yuji YamamotoStatistical Genetics, Osaka University, Suita, Osaka, Japan.ORCID 0000-0002-5489-5079
Penn Medicine BiobankPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Regeneron Genetics CenterPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Global Biobank Meta-Analysis InitiativePathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Sinead ChapmanBroad Institute, Cambridge, MA, United States.ORCID 0000-0002-9454-2737
Wei ZhouBroad Institute, Cambridge, MA, United States.ORCID 0000-0001-7719-0859
Todd EdwardsDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0003-4318-6119
Suneeta SenapatiDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.
Digna R Velez EdwardsDivision of Quantitative Science, Department of Obstetrics and Gynecology, Department of Microbiology, Immunology, and Physiology, Vanderbilt University Medical Center, Nashville, Tennessee, United States.ORCID 0000-0001-5293-0056
Shefali Setia-VermaPathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.ORCID 0000-0001-5216-4670
Funding
Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4MGenomic Basis of Susceptibility to COVID-19 Infection and its ComplicationsU01HG006379 · NHGRI · MAYO CLINIC ROCHESTER · PI Richard R. Sharp · 2011 to 2026
$16.5MFinding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6MVariation, Function, and Disease Supplement ProgramU01HG008657 · NHGRI · UNIVERSITY OF WASHINGTON · PI David Russell Crosslin, Gail Pairitz Jarvik · 2015 to 2026
$13.4MOMOP information model for eMERGE phenotypingU01HG008680 · NHGRI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wendy K Chung, GEORGE M HRIPCSAK · 2015 to 2026
$13.3MDNA Sequencing Support for the eMERGE NetworkU01HG008664 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2015 to 2019
$10.9MGlobal Alliance for Genomic Health (GA4GH)U01HG008676 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI LENNON, NIALL JOHN, REHM, HEIDI L · 2015 to 2019
$8.6MThe Electronic Medical Records and Genomics (eMERGE) Network Phase III Coordinating Center (U01)U01HG008701 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PETERSON, JOSEPH F. · 2015 to 2019
$7.1MVGER, the Vanderbilt Genome-Electronic Records ProjectU01HG008672 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C., RODEN, DAN M · 2015 to 2019
$5.1MThe Future of Genomics Medicine in Patient Care: Contributions from CHOPU01HG008684 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2015 to 2019
$5.0MOMOP information model for eMERGE phenotypingU01HG008679 · NHGRI · GEISINGER CLINIC · PI WILLIAMS, MARC S. · 2015 to 2019
$4.4MBetter Outcomes for Children: Promoting Excellence in Healthcare Genomics to Inform PolicyU01HG008666 · NHGRI · CINCINNATI CHILDRENS HOSP MED CTR · PI HARLEY, JOHN BARKER · 2015 to 2019
$4.2MNCATS NIH HHS UL1 TR001878NHGRI NIH HHS U01 HG006379NHGRI NIH HHS U01 HG008657NHGRI NIH HHS U01 HG008664NHGRI NIH HHS U01 HG008666NHGRI NIH HHS U01 HG008672NHGRI NIH HHS U01 HG008673NHGRI NIH HHS U01 HG008676NHGRI NIH HHS U01 HG008679NHGRI NIH HHS U01 HG008680NHGRI NIH HHS U01 HG008684NHGRI NIH HHS U01 HG008685NHGRI NIH HHS U01 HG008701NICHD NIH HHS R01 HD110567
Abstract
We report the findings of a genome-wide association study (GWAS) meta-analysis of endometriosis across 14 biobanks worldwide, including 32% non-European patient participants, as part of the Global Biobank Meta-Analysis Initiative (GBMI). Out of 58 total loci (29 previously unreported), the largest meta-analysis accounted for 46 (20 previously unreported). We detected the first genome-wide significant loci (
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.