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Submitted on January 27, 2005
Accepted on March 4, 2005
National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA; Section of General Internal Medicine, Boston University School of Medicine, Boston, MA; Departments of Biostatistics and Neurology, Boston University Schools of Public Health and Medicine, Boston, MA; National Heart, Lung and Blood Institute, Bethseda, MD; Department of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Endocrinology, Diabetes, and Medical Genetics, Medical University of South Carolina, Charleston, SC
* To whom correspondence should be addressed. E-mail: Murabito{at}bu.edu.
Background. Twin registries and family history studies provide evidence that genetic factors contribute to the onset of menopause, but heritability estimates in population-based samples are limited. We sought to estimate heritability of age at natural menopause in women participating in the multi-generational Framingham Heart Study, a community-based epidemiologic study.
Methods: 1500 original cohort and 932 offspring cohort women from 1296 extended families reported a natural menopause defined as the natural cessation of menses for one year or more. Correlation coefficients were calculated using FCOR in S.A.G.E. for mother-daughter, sister-sister, and aunt-niece pairs. Heritability was estimated using variance-components methods in SOLAR. Covariates in the multivariable models included generation, number of cigarettes smoked, body mass index, and parity.
Results: The mean age at natural menopause was 49.1 and 49.4 yr in original cohort and offspring women respectively. The multivariable adjusted correlation coefficients for mother-daughter, sister-sister and aunt-niece pairs were 0.21, 0.22, and 0.12 respectively. The crude and multivariable adjusted heritability estimates for age at natural menopause were 0.49 (0.37, 0.61) and 0.52 (0.35, 0.69).
Conclusions: Our data suggests that at least 50% of the inter-individual variability in menopausal age appears to be attributable to genetic effects.
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