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