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 multigenerational Framingham Heart Study, a community-based epidemiological study. METHODS: 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. 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 suggest that at least 50% of the interindividual variability in menopausal age appears to be attributable to genetic effects.
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 multigenerational Framingham Heart Study, a community-based epidemiological study. METHODS: 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. 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 suggest that at least 50% of the interindividual variability in menopausal age appears to be attributable to genetic effects.
Authors: Susan E Appt; Haiying Chen; Amanda K Goode; Patricia B Hoyer; Thomas B Clarkson; Michael R Adams; Mark E Wilson; Adrian A Franke; Jay R Kaplan Journal: Menopause Date: 2010-07 Impact factor: 2.953
Authors: Chunyan He; Peter Kraft; Daniel I Chasman; Julie E Buring; Constance Chen; Susan E Hankinson; Guillaume Paré; Stephen Chanock; Paul M Ridker; David J Hunter Journal: Hum Genet Date: 2010-08-24 Impact factor: 4.132
Authors: Kathryn J Ruddy; Daniel J Schaid; Ann H Partridge; Nicholas B Larson; Anthony Batzler; Lothar Häberle; Ralf Dittrich; Peter Widschwendter; Visnja Fink; Emanuel Bauer; Judith Schwitulla; Matthias Rübner; Arif B Ekici; Viktoria Aivazova-Fuchs; Elizabeth A Stewart; Matthias W Beckmann; Elizabeth Ginsburg; Liewei Wang; Richard M Weinshilboum; Fergus J Couch; Wolfgang Janni; Brigitte Rack; Celine Vachon; Peter A Fasching Journal: Fertil Steril Date: 2019-07-29 Impact factor: 7.329
Authors: Lisette Stolk; Guangju Zhai; Joyce B J van Meurs; Michael M P J Verbiest; Jenny A Visser; Karol Estrada; Fernando Rivadeneira; Frances M Williams; Lynn Cherkas; Panos Deloukas; Nicole Soranzo; Jules J de Keyzer; Victor J M Pop; Paul Lips; Corinne E I Lebrun; Yvonne T van der Schouw; Diederick E Grobbee; Jacqueline Witteman; Albert Hofman; Huibert A P Pols; Joop S E Laven; Tim D Spector; André G Uitterlinden Journal: Nat Genet Date: 2009-05-17 Impact factor: 38.330
Authors: Chunyan He; Peter Kraft; Constance Chen; Julie E Buring; Guillaume Paré; Susan E Hankinson; Stephen J Chanock; Paul M Ridker; David J Hunter; Daniel I Chasman Journal: Nat Genet Date: 2009-05-17 Impact factor: 38.330