TY - JOUR T1 - A genome-wide association study of early menopause and the combined impact of identified variants. JF - Hum Mol Genet Y1 - 2013 A1 - Perry, John R B A1 - Corre, Tanguy A1 - Esko, Tõnu A1 - Chasman, Daniel I A1 - Fischer, Krista A1 - Franceschini, Nora A1 - He, Chunyan A1 - Kutalik, Zoltán A1 - Mangino, Massimo A1 - Rose, Lynda M A1 - Vernon Smith, Albert A1 - Stolk, Lisette A1 - Sulem, Patrick A1 - Weedon, Michael N A1 - Zhuang, Wei V A1 - Arnold, Alice A1 - Ashworth, Alan A1 - Bergmann, Sven A1 - Buring, Julie E A1 - Burri, Andrea A1 - Chen, Constance A1 - Cornelis, Marilyn C A1 - Couper, David J A1 - Goodarzi, Mark O A1 - Gudnason, Vilmundur A1 - Harris, Tamara A1 - Hofman, Albert A1 - Jones, Michael A1 - Kraft, Peter A1 - Launer, Lenore A1 - Laven, Joop S E A1 - Li, Guo A1 - McKnight, Barbara A1 - Masciullo, Corrado A1 - Milani, Lili A1 - Orr, Nicholas A1 - Psaty, Bruce M A1 - Ridker, Paul M A1 - Rivadeneira, Fernando A1 - Sala, Cinzia A1 - Salumets, Andres A1 - Schoemaker, Minouk A1 - Traglia, Michela A1 - Waeber, Gérard A1 - Chanock, Stephen J A1 - Demerath, Ellen W A1 - Garcia, Melissa A1 - Hankinson, Susan E A1 - Hu, Frank B A1 - Hunter, David J A1 - Lunetta, Kathryn L A1 - Metspalu, Andres A1 - Montgomery, Grant W A1 - Murabito, Joanne M A1 - Newman, Anne B A1 - Ong, Ken K A1 - Spector, Tim D A1 - Stefansson, Kari A1 - Swerdlow, Anthony J A1 - Thorsteinsdottir, Unnur A1 - van Dam, Rob M A1 - Uitterlinden, André G A1 - Visser, Jenny A A1 - Vollenweider, Peter A1 - Toniolo, Daniela A1 - Murray, Anna KW - Case-Control Studies KW - Female KW - Gene Frequency KW - Genome-Wide Association Study KW - Humans KW - Menopause, Premature KW - Polymorphism, Single Nucleotide KW - Primary Ovarian Insufficiency KW - Quantitative Trait Loci KW - Risk AB -

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.

VL - 22 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23307926?dopt=Abstract ER -