A genome-wide association study of early menopause and the combined impact of identified variants.
Vernon Smith, A
Van Dam, RM
Human Molecular Genetics
Oxford University Press (OUP)
© The Author 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact firstname.lastname@example.org.
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.
J.R.B.P. is funded by the Wellcome Trust as a Sir Henry Wellcome Postdoctoral Research Fellow (092447/Z/10/Z). Funding details for individual studies is provided in supplementary information. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.
This is the final version of the article. Available from the publisher via the DOI in this record.
Vol. 22, pp. 1465 - 1472
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