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Nat Commun. 2017 May 24;8:15539. doi: 10.1038/ncomms15539.

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

Author information

1
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
2
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
3
deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
4
Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
5
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
6
KULeuven, Department of Development and Regeneration, Organ systems, 3000 Leuven, Belgium.
7
Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospital Leuven, 3000 Leuven, Belgium.
8
Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
9
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
10
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
11
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
12
Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
13
Vanderbilt Genetics Institute, Division of Epidemiology, Institute of Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
14
Cognitive Science Department, University of California, San Diego, La Jolla, California 92093, USA.
15
Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
16
Endometriosis CaRe Centre, Nuffield Dept of Obstetrics &Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
17
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-2181, Japan.
18
Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
19
Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
20
Department of Obstetrics and Gynecology, Landspitali University Hospital, 101 Reykjavik, Iceland.
21
Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
22
Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute of Medicine and Public Health, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
23
Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
24
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, DK-2100 Copenhagen, Denmark.
25
Global Medical Affairs Fertility, Research and Development, Merck KGaA, Darmstadt, Germany.
26
23andMe, Inc., 899 W. Evelyn Avenue, Mountain View, California 94041, USA.
27
Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland 4059, Australia.

Abstract

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.

PMID:
28537267
PMCID:
PMC5458088
DOI:
10.1038/ncomms15539
[Indexed for MEDLINE]
Free PMC Article

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