A genome-wide association study of early menopause and the combined impact of identified variants
Year: 2013
Type: article
Abstract: 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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/dds551
Authors: 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
Institutions: Centre for Human Genetics, King's College London, University of Exeter, University of Oxford, SIB Swiss Institute of Bioinformatics, IRCCS Ospedale San Raffaele, University of Lausanne, Institute of Molecular and Cell Biology, Brigham and Women's Hospital, Harvard University, Indiana University Indianapolis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, University of Iceland, Icelandic Heart Association, Netherlands Consortium for Healthy Ageing, deCODE Genetics (Iceland), Boston University, Institute of Cancer Research, University of North Carolina at Chapel Hill, Cedars-Sinai Medical Center, National Institutes of Health, Erasmus MC, University of Washington, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute, Competence Centre on Health Technologies (Estonia), University of Tartu, Centre Hospitalier Universitaire Vaudois, Division of Cancer Epidemiology and Genetics, University of Minnesota, QIMR Berghofer Medical Research Institute, Framingham Heart Study, University of Pittsburgh, University of Cambridge, Addenbrooke's Hospital, MRC Epidemiology Unit, Medical Research Council, National University of Singapore, Istituto di Genetica Molecolare
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
OpenAlex ID: W2101474847