Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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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PMID
31649266
TITLE
Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.
ABSTRACT
Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10 ) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
DATE PUBLISHED
2019 10 24
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/02/28
accepted 2019/09/10
entrez 2019/10/26 06:00
pubmed 2019/10/28 06:00
medline 2020/02/06 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gallagher CS Gallagher C S CS Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Mäkinen N Mäkinen N N Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. netta_makinen@dfci.harvard.edu.
Harris HR Harris H R HR Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Rahmioglu N Rahmioglu N N Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Uimari O Uimari O O Department of Obstetrics and Gynecology, Oulu University Hospital and PEDEGO Research Unit & Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90220, Oulu, Finland.
Cook JP Cook J P JP Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK.
Shigesi N Shigesi N N Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Ferreira T Ferreira T T Big Data Institute, Li Ka Shing Center for Health Information and Discovery, Oxford University, Oxford, OX3 7LF, UK.
Velez-Edwards DR Velez-Edwards D R DR Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, 37203, USA.
Edwards TL Edwards T L TL Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37203, USA.
Mortlock S Mortlock S S Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia.
Ruhioglu Z Ruhioglu Z Z Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Day F Day F F MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Becker CM Becker C M CM Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Karhunen V Karhunen V V Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, UK.
Martikainen H Martikainen H H Department of Obstetrics and Gynecology, Oulu University Hospital and PEDEGO Research Unit & Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90220, Oulu, Finland.
Järvelin MR Järvelin M-R MR Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, Middlesex, UB8 3PH, UK.
Cantor RM Cantor R M RM Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
Ridker PM Ridker P M PM Division of Preventative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Terry KL Terry K L KL Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
Buring JE Buring J E JE Division of Preventative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gordon SD Gordon S D SD Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Medland SE Medland S E SE Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Montgomery GW Montgomery G W GW Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Nyholt DR Nyholt D R DR Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
Hinds DA Hinds D A DA 23andMe, Mountain View, CA, 94041, USA.
Tung JY Tung J Y JY 23andMe, Mountain View, CA, 94041, USA.
23andMe Research Team
Perry JRB Perry J R B JRB MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Lind PA Lind P A PA Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Painter JN Painter J N JN Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Martin NG Martin N G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Morris AP Morris A P AP Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK.
Chasman DI Chasman D I DI Division of Preventative Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Missmer SA Missmer S A SA Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA.
Zondervan KT Zondervan K T KT Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Morton CC Morton C C CC Manchester Centre for Audiology and Deafness, Manchester Academic Health Science Center, University of Manchester, Manchester, M13 9PL, UK. cmorton@bwh.harvard.edu.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Agee Michelle M
Alipanahi Babak B
Auton Adam A
Bell Robert K RK
Bryc Katarzyna K
Elson Sarah L SL
Fontanillas Pierre P
Furlotte Nicholas A NA
Huber Karen E KE
Kleinman Aaron A
Litterman Nadia K NK
McIntyre Matthew H MH
Mountain Joanna L JL
Noblin Elizabeth S ES
Northover Carrie A M CAM
Pitts Steven J SJ
Sathirapongsasuti J Fah JF
Sazonova Olga V OV
Shelton Janie F JF
Shringarpure Suyash S
Tian Chao C
Vacic Vladimir V
Wilson Catherine H CH
JOURNAL
VOLUME: 10
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2019
MONTH: 10
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
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Ataxia Telangiectasia Mutated Proteins genetics
Endometriosis genetics
European Continental Ancestry Group genetics
Female genetics
Forkhead Box Protein O1 metabolism
Genome-Wide Association Study metabolism
Humans metabolism
Leiomyoma genetics
Mendelian Randomization Analysis genetics
Menorrhagia etiology
Middle Aged etiology
Polymorphism, Single Nucleotide etiology
Proportional Hazards Models etiology
Receptor, Fibroblast Growth Factor, Type 4 genetics
Signal Transduction genetics
Telomerase genetics
Uterine Neoplasms genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 FOXO1 protein, human
0 Forkhead Box Protein O1
EC 2.7.10.1 FGFR4 protein, human
EC 2.7.10.1 Receptor, Fibroblast Growth Factor, Type 4
EC 2.7.11.1 ATM protein, human
EC 2.7.11.1 Ataxia Telangiectasia Mutated Proteins
EC 2.7.7.49 TERT protein, human
EC 2.7.7.49 Telomerase
OTHER ID's