Heritability of age at natural menopause in the Framingham Heart Study

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 multigenerational Framingham Heart Study, a community-based epidemiological study.

A total of 1500 original cohort and 932 offspring cohort women from 1296 extended families reported a natural menopause defined as the natural cessation of menses for 1 yr or more. Correlation coefficients were calculated using family correlations in Statistical Applications for Genetic Epidemiology for mother-daughter, sister-sister, and aunt-niece pairs. Heritability was estimated using variance-components methods in the Sequential Oligogenic Linkage Analysis Routines (SOLAR) computer package. Covariates in the multivariable models included generation, number of cigarettes smoked, body mass index, and parity.

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).

Our data suggest that at least 50% of the interindividual variability in menopausal age appears to be attributable to genetic effects.