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

TitleA genome-wide association study of early menopause and the combined impact of identified variants.
Publication TypeJournal Article
Year of Publication2013
AuthorsPerry, JRB, Corre, T, Esko, T, Chasman, DI, Fischer, K, Franceschini, N, He, C, Kutalik, Z, Mangino, M, Rose, LM, Smith, AVernon, Stolk, L, Sulem, P, Weedon, MN, Zhuang, WV, Arnold, A, Ashworth, A, Bergmann, S, Buring, JE, Burri, A, Chen, C, Cornelis, MC, Couper, DJ, Goodarzi, MO, Gudnason, V, Harris, T, Hofman, A, Jones, M, Kraft, P, Launer, L, Laven, JSE, Li, G, McKnight, B, Masciullo, C, Milani, L, Orr, N, Psaty, BM, Ridker, PM, Rivadeneira, F, Sala, C, Salumets, A, Schoemaker, M, Traglia, M, Waeber, G, Chanock, SJ, Demerath, EW, Garcia, M, Hankinson, SE, Hu, FB, Hunter, DJ, Lunetta, KL, Metspalu, A, Montgomery, GW, Murabito, JM, Newman, AB, Ong, KK, Spector, TD, Stefansson, K, Swerdlow, AJ, Thorsteinsdottir, U, van Dam, RM, Uitterlinden, AG, Visser, JA, Vollenweider, P, Toniolo, D, Murray, A
Corporate/Institutional AuthorsReproGen Consortium
JournalHum Mol Genet
Date Published2013 Apr 01
KeywordsCase-Control Studies, Female, Gene Frequency, Genome-Wide Association Study, Humans, Menopause, Premature, Polymorphism, Single Nucleotide, Primary Ovarian Insufficiency, Quantitative Trait Loci, Risk
Abstract<p>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.</p>
Alternate JournalHum. Mol. Genet.
PubMed ID23307926
PubMed Central IDPMC3596848
Grant ListR01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
MC_UU_12015/2 / / Medical Research Council / United Kingdom
MC_U106179472 / / Medical Research Council / United Kingdom
R01 CA047988 / CA / NCI NIH HHS / United States