A genome-wide association study of early menopause and the combined impact of identified variants

John R.B. Perry; Tanguy Corre; Tõnu Esko; Daniel I. Chasman; Krista Fischer; Nora Franceschini; Chunyan He; Zoltan Kutalik; Massimo Mangino; Lynda M. Rose; Albert Vernon smith; Lisette Stolk; Patrick Sulem; Michael N. Weedon; Wei V. Zhuang; Alice Arnold; Alan Ashworth; Sven Bergmann; Julie E. Buring; Andrea Burri; Constance Chen; Marilyn C. Cornelis; David J. Couper; Mark O. Goodarzi; Vilmundur Gudnason; Tamara Harris; Albert Hofman; Michael Jones; Peter Kraft; Lenore Launer; Joop S.E. Laven; Guo Li; Barbara Mcknight; Corrado Masciullo; Lili Milani; Nicholas Orr; Bruce M. Psaty; Paul M. Ridker; Fernando Rivadeneira; Cinzia Sala; Andres Salumets; Minouk Schoemaker; Michela Traglia; Gérard Waeber; Stephen J. Chanock; Ellen W. Demerath; Melissa Garcia; Susan E. Hankinson; Frank B. Hu; David J. Hunter; Kathryn L. Lunetta; Andres Metspalu; Grant W. Montgomery; Joanne M. Murabito; Anne B. Newman; Ken K. Ong; Tim D. Spector; Kari Stefansson; Anthony J. Swerdlow; Unnur Thorsteinsdottir; Rob M. Van dam; André G. Uitterlinden; Jenny A. Visser; Peter Vollenweider; Daniela Toniolo; Anna Murray

doi:10.1093/hmg/dds551

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A genome-wide association study of early menopause and the combined impact of identified variants

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A genome-wide association study of early menopause and the combined impact of identified variants

John R.B. Perry, Tanguy Corre, Tõnu Esko, Daniel I. Chasman, Krista Fischer, Nora Franceschini, Chunyan He, Zoltan Kutalik, Massimo Mangino, Lynda M. Rose, …

Human Molecular Genetics, Vol.22(7), pp.1465-1472

04/2013

DOI: https://doi.org/10.1093/hmg/dds551

PMCID: PMC3596848

PMID: 23307926

Abstract

Molecular Biology

Genetics

Genetics(clinical)

Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ~30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.

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Title: A genome-wide association study of early menopause and the combined impact of identified variants
Creators: John R.B. Perry (Author) - University of Exeter;University of Oxford;King's College London
Tanguy Corre (Author) - University of Lausanne;Swiss Institute of Bioinformatics;IRCCS San Raffaele Scientific Institute
Tõnu Esko (Author) - Estonian Biocentre;University of Tartu
Daniel I. Chasman (Author) - Harvard University
Krista Fischer (Author) - Estonian Biocentre
Nora Franceschini (Author) - University of North Carolina at Chapel Hill
Chunyan He (Author) - Indiana University Bloomington
Zoltan Kutalik (Author) - University of Lausanne;Swiss Institute of Bioinformatics
Massimo Mangino (Author) - King's College London
Lynda M. Rose (Author) - Harvard University
Albert Vernon smith (Author) - Icelandic Heart Association;University of Iceland
Lisette Stolk (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Aging
Patrick Sulem (Author) - deCODE Genetics
Michael N. Weedon (Author) - University of Exeter
Wei V. Zhuang (Author) - Public Health
Alice Arnold (Author) - University of Washington
Alan Ashworth (Author) - Institute of Cancer Research
Sven Bergmann (Author) - University of Lausanne;Swiss Institute of Bioinformatics
Julie E. Buring (Author) - Harvard University
Andrea Burri (Author) - King's College London
Constance Chen (Author) - Harvard University
Marilyn C. Cornelis (Author) - Harvard University
David J. Couper (Author) - University of North Carolina at Chapel Hill
Mark O. Goodarzi (Author) - Cedars-Sinai Medical Center
Vilmundur Gudnason (Author) - Icelandic Heart Association;University of Iceland
Tamara Harris (Author) - National Institutes of Health, Bethesda
Albert Hofman (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Aging
Michael Jones (Author) - Institute of Cancer Research
Peter Kraft (Author) - Harvard University
Lenore Launer (Author) - National Institutes of Health, Bethesda
Joop S.E. Laven (Author) - Erasmus University Rotterdam
Guo Li (Author) - University of Washington
Barbara Mcknight (Author) - University of Washington
Corrado Masciullo (Author) - IRCCS San Raffaele Scientific Institute
Lili Milani (Author) - Estonian Biocentre
Nicholas Orr (Author) - Institute of Cancer Research
Bruce M. Psaty (Author) - University of Washington;Group Health Cooperative
Paul M. Ridker (Author) - Harvard University
Fernando Rivadeneira (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Aging
Cinzia Sala (Author) - IRCCS San Raffaele Scientific Institute
Andres Salumets (Author) - University of Tartu;Competence Centre on Reproductive Medicine and Biology
Minouk Schoemaker (Author) - Institute of Cancer Research
Michela Traglia (Author) - IRCCS San Raffaele Scientific Institute
Gérard Waeber (Author) - University of Lausanne
Stephen J. Chanock (Author) - National Institutes of Health
Ellen W. Demerath (Author) - University of Minnesota Twin Cities
Melissa Garcia (Author) - National Institutes of Health, Bethesda
Susan E. Hankinson (Author) - Harvard University
Frank B. Hu (Author) - Harvard University
David J. Hunter (Author) - Harvard University
Kathryn L. Lunetta (Author) - Boston University
Andres Metspalu (Author) - Estonian Biocentre;University of Tartu
Grant W. Montgomery (Author) - Queensland Institute of Medical Research
Joanne M. Murabito (Author) - National Heart, Lung, and Blood Institute's The Framingham Heart Study;Boston University
Anne B. Newman (Author) - University of Pittsburgh
Ken K. Ong (Author) - Cambridge University Hospitals NHS Foundation Trust;University of Cambridge
Tim D. Spector (Author) - King's College London
Kari Stefansson (Author) - deCODE Genetics
Anthony J. Swerdlow (Author) - Institute of Cancer Research
Unnur Thorsteinsdottir (Author) - deCODE Genetics
Rob M. Van dam (Author) - Harvard University;National University of Singapore
André G. Uitterlinden (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Aging
Jenny A. Visser (Author) - Erasmus University Rotterdam
Peter Vollenweider (Author) - University of Lausanne
Daniela Toniolo (Author) - IRCCS San Raffaele Scientific Institute;Institute of Molecular Genetics
Anna Murray (Author) - University of Exeter
Publication Details: Human Molecular Genetics, Vol.22(7), pp.1465-1472
Series: 22
Number of pages: 8
Identifiers: 991005930707202656
Academic Unit: Master Public Health
Language: English
Resource Type: Journal article