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A genome-wideassociation study ofearly menopause andthe combined impactof identifiedvariants John R. B. PerryTanguy CorreTõnu Esko2013 год

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

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Аннотация: 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.
Год издания: 2013
Авторы: John R. B. Perry, Tanguy Corre, Tõnu Esko, Daniel I. Chasman, Krista Fischer, Nora Franceschini, Chunyan He, Zoltán Kutalik, Massimo Mangino, Lynda M. Rose, Albert V. Smith, Lisette Stolk, Patrick Sulem, Michael N. Weedon, Wei Vivian Zhuang, Alice M. Arnold, Alan Ashworth, Sven Bergmann, Julie E. Buring, Andrea Burri, Constance Chen, Marilyn C. Cornelis, David Couper, Mark O. Goodarzi, Vilmundur Guðnason, Tamara Harris, Albert Hofman, Michael E. Jones, Peter Kraft, Lenore J. Launer, Joop S.E. Laven, Guo Li, Barbara McKnight, Corrado Masciullo, Lili Milani, Nick Orr, Bruce M. Psaty, Paul M. Ridker, Fernando Rivadeneira, Cinzia Sala, Andres Salumets, Minouk J. Schoemaker, Michela Traglia, Gérard Waeber, Stephen J. Chanock, Ellen W. Demerath, Melissa García, 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, Kári Stéfansson, Anthony J. Swerdlow, Unnur Þorsteinsdóttir, Rob M. van Dam, André G. Uitterlinden, Jenny A. Visser, Péter Vollenweider, Daniela Toniolo, Anna Murray
Издательство: Oxford University Press
Источник: Human Molecular Genetics
Ключевые слова: Estrogen and related hormone effects, Sex and Gender in Healthcare, Menopause: Health Impacts and Treatments
Другие ссылки: Human Molecular Genetics (PDF)
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Europe PMC (PubMed Central) (PDF)
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Digital Access to Scholarship at Harvard (DASH) (Harvard University) (PDF)
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