Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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28537267
TITLE
Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism.
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.
DATE PUBLISHED
2017 May 24
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/11/11
accepted 2017/04/07
entrez 2017/05/25 06:00
pubmed 2017/05/26 06:00
medline 2017/05/26 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Sapkota Y Sapkota Yadav Y Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Steinthorsdottir V Steinthorsdottir Valgerdur V deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
Morris AP Morris Andrew P AP Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Fassbender A Fassbender Amelie A Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospital Leuven, 3000 Leuven, Belgium.
Rahmioglu N Rahmioglu Nilufer N Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
De Vivo I De Vivo Immaculata I Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Buring JE Buring Julie E JE Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
Zhang F Zhang Futao F Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Edwards TL Edwards Todd L TL Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
Jones S Jones Sarah S Vanderbilt Genetics Institute, Division of Epidemiology, Institute of Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
O D O Dorien D Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospital Leuven, 3000 Leuven, Belgium.
Peterse D Peterse Daniëlle D Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospital Leuven, 3000 Leuven, Belgium.
Rexrode KM Rexrode Kathryn M KM Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
Ridker PM Ridker Paul M PM Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
Schork AJ Schork Andrew J AJ Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
MacGregor S MacGregor Stuart S Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
Martin NG Martin Nicholas G NG Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
Becker CM Becker Christian M CM Endometriosis CaRe Centre, Nuffield Dept of Obstetrics &Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Adachi S Adachi Sosuke S Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-2181, Japan.
Yoshihara K Yoshihara Kosuke K Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-2181, Japan.
Enomoto T Enomoto Takayuki T Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-2181, Japan.
Takahashi A Takahashi Atsushi A Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Kamatani Y Kamatani Yoichiro Y Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Matsuda K Matsuda Koichi K Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
Kubo M Kubo Michiaki M Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Thorleifsson G Thorleifsson Gudmar G deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
Geirsson RT Geirsson Reynir T RT Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
Thorsteinsdottir U Thorsteinsdottir Unnur U Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
Wallace LM Wallace Leanne M LM Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
iPSYCH-SSI-Broad Group
Yang J Yang Jian J Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Velez Edwards DR Velez Edwards Digna R DR 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.
Nyegaard M Nyegaard Mette M iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, DK-2100 Copenhagen, Denmark.
Low SK Low Siew-Kee SK Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Zondervan KT Zondervan Krina T KT Endometriosis CaRe Centre, Nuffield Dept of Obstetrics &Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Missmer SA Missmer Stacey A SA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
D'Hooghe T D'Hooghe Thomas T Global Medical Affairs Fertility, Research and Development, Merck KGaA, Darmstadt, Germany.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Chasman DI Chasman Daniel I DI Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
Stefansson K Stefansson Kari K Faculty of Medicine, School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
Tung JY Tung Joyce Y JY 23andMe, Inc., 899 W. Evelyn Avenue, Mountain View, California 94041, USA.
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland 4059, Australia.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Werge Thomas M TM
Thompson Wesley K WK
JOURNAL
VOLUME: 8
ISSUE:
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2017
MONTH: May
DAY: 24
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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