Common genetic variants are significant risk factors for early menopause: results from the breakthrough generations study
Common genetic variants are significant risk factors for early menopause: results from the breakthrough generations study
Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators. Age at menopause and early menopause (EM) are highly heritable, suggesting a genetic aetiology. Recent genome-wide scans have identified four loci associated with variation in the age of normal menopause (40–60 years). We aimed to determine whether theses loci are also risk factors for EM. We tested the four menopause-associated genetic variants in a cohort of approximately 2000 women with menopause ?45 years from the Breakthrough Generations Study (BGS). All four variants significantly increased the odds of having EM. Comparing the 4.5% of individuals with the lowest number of risk alleles (two or three) with the 3.0% with the highest number (eight risk alleles), the odds ratio was 4.1 (95% CI 2.4–7.1, P = 4.0 × 10?7). In combination, the four variants discriminated EM cases with a receiver operator characteristic area under the curve of 0.6. Four common genetic variants identified by genome-wide association studies, had a significant impact on the odds of having EM in an independent cohort from the BGS. The discriminative power is still limited, but as more variants are discovered they may be useful for predicting reproductive lifespan.
186-192
Murray, Anna
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Bennett, Claire E.
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Perry, John R.B.
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Weedon, Michael N.
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Jacobs, Patricia A.
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Morris, Danielle H.
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Orr, Nicholas
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Schoemaker, Minouk J.
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Jones, Michael
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Ashworth, Alan
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Swerdlow, Anthony J.
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1 January 2011
Murray, Anna
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Bennett, Claire E.
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Perry, John R.B.
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Weedon, Michael N.
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Jacobs, Patricia A.
d87ec15b-13c3-4868-96f1-b4b99030fa5b
Morris, Danielle H.
09ed485b-faca-424c-a838-bfdf2da50ba5
Orr, Nicholas
ea5ee90f-8f1a-4e56-9f55-c9300f02cfb2
Schoemaker, Minouk J.
d6949f41-d64c-4b46-aedb-d6a87c36797f
Jones, Michael
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Ashworth, Alan
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Swerdlow, Anthony J.
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Murray, Anna, Bennett, Claire E., Perry, John R.B., Weedon, Michael N., Jacobs, Patricia A., Morris, Danielle H., Orr, Nicholas, Schoemaker, Minouk J., Jones, Michael, Ashworth, Alan and Swerdlow, Anthony J.
(2011)
Common genetic variants are significant risk factors for early menopause: results from the breakthrough generations study.
Human Molecular Genetics, 20 (1), .
(doi:10.1093/hmg/ddq417).
(PMID:20952801)
Abstract
Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators. Age at menopause and early menopause (EM) are highly heritable, suggesting a genetic aetiology. Recent genome-wide scans have identified four loci associated with variation in the age of normal menopause (40–60 years). We aimed to determine whether theses loci are also risk factors for EM. We tested the four menopause-associated genetic variants in a cohort of approximately 2000 women with menopause ?45 years from the Breakthrough Generations Study (BGS). All four variants significantly increased the odds of having EM. Comparing the 4.5% of individuals with the lowest number of risk alleles (two or three) with the 3.0% with the highest number (eight risk alleles), the odds ratio was 4.1 (95% CI 2.4–7.1, P = 4.0 × 10?7). In combination, the four variants discriminated EM cases with a receiver operator characteristic area under the curve of 0.6. Four common genetic variants identified by genome-wide association studies, had a significant impact on the odds of having EM in an independent cohort from the BGS. The discriminative power is still limited, but as more variants are discovered they may be useful for predicting reproductive lifespan.
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Accepted/In Press date: 17 October 2010
Published date: 1 January 2011
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Local EPrints ID: 166441
URI: http://eprints.soton.ac.uk/id/eprint/166441
PURE UUID: 579073bf-a242-4da0-a75b-ecb4384c4f86
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Date deposited: 28 Oct 2010 13:50
Last modified: 14 Mar 2024 02:13
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Contributors
Author:
Anna Murray
Author:
Claire E. Bennett
Author:
John R.B. Perry
Author:
Michael N. Weedon
Author:
Patricia A. Jacobs
Author:
Danielle H. Morris
Author:
Nicholas Orr
Author:
Minouk J. Schoemaker
Author:
Michael Jones
Author:
Alan Ashworth
Author:
Anthony J. Swerdlow
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