Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometrio...

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Bibliographic Details
Published in:Nature communications Vol. 8; no. 1; pp. 15539 - 12
Main Authors: Sapkota, Yadav, Steinthorsdottir, Valgerdur, Morris, Andrew P., Fassbender, Amelie, Rahmioglu, Nilufer, De Vivo, Immaculata, Buring, Julie E., Zhang, Futao, Edwards, Todd L., Jones, Sarah, O, Dorien, Peterse, Daniëlle, Rexrode, Kathryn M., Ridker, Paul M., Schork, Andrew J., MacGregor, Stuart, Martin, Nicholas G., Becker, Christian M., Adachi, Sosuke, Yoshihara, Kosuke, Enomoto, Takayuki, Takahashi, Atsushi, Kamatani, Yoichiro, Matsuda, Koichi, Kubo, Michiaki, Thorleifsson, Gudmar, Geirsson, Reynir T., Thorsteinsdottir, Unnur, Wallace, Leanne M., Yang, Jian, Velez Edwards, Digna R., Nyegaard, Mette, Low, Siew-Kee, Zondervan, Krina T., Missmer, Stacey A., D'Hooghe, Thomas, Montgomery, Grant W., Chasman, Daniel I., Stefansson, Kari, Tung, Joyce Y., Nyholt, Dale R.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 24.05.2017
Nature Publishing Group
Nature Portfolio
Subjects:
38/47
45/43
631/208/205/2138
631/208/457/649
692/308/2056
692/499
Adult
Aged
Endometriosis
Endometriosis - genetics
Endometriosis - metabolism
Epidemiology
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Female
Fertility
Genetic Loci - genetics
Genetic Predisposition to Disease
Genetics
Genome-Wide Association Study
Genomes
Genotype
Gonadal Steroid Hormones - metabolism
Gynecology
Health care
Hospitals
Humanities and Social Sciences
Humans
Meta-analysis
Metabolic Networks and Pathways - genetics
Metabolism
Middle Aged
multidisciplinary
Obstetrics
Polymorphism, Single Nucleotide
Preventive medicine
Public health
R&D
Research & development
Science
Science (multidisciplinary)
Steroids
United Kingdom > UK
Queensland Australia
United States > US
Tennessee
Japan
California
Iceland
Nashville Tennessee
Belgium
Massachusetts
Denmark
Australia
Aarhus Denmark
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk ( P <5 × 10 −8 ), implicating genes involved in sex steroid hormone pathways ( FN1 , CCDC170 , ESR1 , SYNE1 and FSHB ). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts. Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.
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These authors contributed equally to this work.
A full list of consortium members appears at the end of the paper.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms15539