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


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.

SUBMITTER: Perry JR 

PROVIDER: S-EPMC3596848 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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

Perry John R B JR   Corre Tanguy T   Esko Tõnu T   Chasman Daniel I DI   Fischer Krista K   Franceschini Nora N   He Chunyan C   Kutalik Zoltan Z   Mangino Massimo M   Rose Lynda M LM   Vernon Smith Albert A   Stolk Lisette L   Sulem Patrick P   Weedon Michael N MN   Zhuang Wei V WV   Arnold Alice A   Ashworth Alan A   Bergmann Sven S   Buring Julie E JE   Burri Andrea A   Chen Constance C   Cornelis Marilyn C MC   Couper David J DJ   Goodarzi Mark O MO   Gudnason Vilmundur V   Harris Tamara T   Hofman Albert A   Jones Michael M   Kraft Peter P   Launer Lenore L   Laven Joop S E JS   Li Guo G   McKnight Barbara B   Masciullo Corrado C   Milani Lili L   Orr Nicholas N   Psaty Bruce M BM   Ridker Paul M PM   Rivadeneira Fernando F   Sala Cinzia C   Salumets Andres A   Schoemaker Minouk M   Traglia Michela M   Waeber Gérard G   Chanock Stephen J SJ   Demerath Ellen W EW   Garcia Melissa M   Hankinson Susan E SE   Hu Frank B FB   Hunter David J DJ   Lunetta Kathryn L KL   Metspalu Andres A   Montgomery Grant W GW   Murabito Joanne M JM   Newman Anne B AB   Ong Ken K KK   Spector Tim D TD   Stefansson Kari K   Swerdlow Anthony J AJ   Thorsteinsdottir Unnur U   Van Dam Rob M RM   Uitterlinden André G AG   Visser Jenny A JA   Vollenweider Peter P   Toniolo Daniela D   Murray Anna A  

Human molecular genetics 20130109 7


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.  ...[more]

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