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

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Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A genome-wide association study of early menopause and the combined impact of identified variants.
Journal
Human Molecular Genetics
Author(s)
Perry J.R., Corre T., Esko T., Chasman D.I., Fischer K., Franceschini N., He C., Kutalik Z., Mangino M., Rose L.M., Vernon Smith A., Stolk L., Sulem P., Weedon M.N., Zhuang W.V., Arnold A., Ashworth A., Bergmann S., Buring J.E., Burri A., Chen C., Cornelis M.C., Couper D.J., Goodarzi M.O., Gudnason V., Harris T., Hofman A., Jones M., Kraft P., Launer L., Laven J.S., Li G., McKnight B., Masciullo C., Milani L., Orr N., Psaty B.M., Ridker P.M., Ridker P.M., Rivadeneira F., Sala C., Salumets A., Schoemaker M., Traglia M., Waeber G., Chanock S.J., Demerath E.W., Garcia M., Hankinson S.E., Hu F.B., Hunter D.J., Lunetta K.L., Metspalu A., Montgomery G.W., Murabito J.M., Newman A.B., Ong K.K., Spector T.D., Stefansson K., Swerdlow A.J., Thorsteinsdottir U., Van Dam R.M., Uitterlinden A.G., Visser J.A., Vollenweider P., Toniolo D., Murray A.
Working group(s)
ReproGen Consortium
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
2013
Volume
22
Number
7
Pages
1465-1472
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
28/03/2013 12:05
Last modification date
20/08/2019 12:52
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