BACKGROUND: Environmental factors explain only a small part of the age variance at which menopause commences. The variation in natural menopause is a trait predominantly determined by interaction of multiple genes, whose identity and causative genetic variation remains to be determined. Menopause is a retrospective marker for the reproductive capacity of preceding years, since subfertility and infertility precede menopause at distinct time-intervals. In the present study we have investigated the contribution of genetic factors to menopausal age. METHODS: Data were collected from a random population sample of singleton and twin sisters participating in a prospective breast cancer screening project, who had subsequently experienced natural menopause. Heritability of menopausal age was estimated with analysis of variance, Mx modelling and Gibbs sampling. RESULTS: All produced almost identical heritability estimates of 0.85-0.87 for singleton sisters, suggesting a strong genetic contribution to menopausal age. Twin data were used to distinguish additive genetic from common environmental effects; a heritability of 0.71-0.72 was determined, which does not deviate significantly from the estimate for singleton sisters. CONCLUSIONS: According to our findings, a woman with a family history of early menopause risks early menopause and consequently early reproductive failure herself.
BACKGROUND: Environmental factors explain only a small part of the age variance at which menopause commences. The variation in natural menopause is a trait predominantly determined by interaction of multiple genes, whose identity and causative genetic variation remains to be determined. Menopause is a retrospective marker for the reproductive capacity of preceding years, since subfertility and infertility precede menopause at distinct time-intervals. In the present study we have investigated the contribution of genetic factors to menopausal age. METHODS: Data were collected from a random population sample of singleton and twin sisters participating in a prospective breast cancer screening project, who had subsequently experienced natural menopause. Heritability of menopausal age was estimated with analysis of variance, Mx modelling and Gibbs sampling. RESULTS: All produced almost identical heritability estimates of 0.85-0.87 for singleton sisters, suggesting a strong genetic contribution to menopausal age. Twin data were used to distinguish additive genetic from common environmental effects; a heritability of 0.71-0.72 was determined, which does not deviate significantly from the estimate for singleton sisters. CONCLUSIONS: According to our findings, a woman with a family history of early menopause risks early menopause and consequently early reproductive failure herself.
Authors: Kristel M van Asselt; Helen S Kok; Hein Putter; Cisca Wijmenga; Petra H M Peeters; Yvonne T van der Schouw; Diederick E Grobbee; Egbert R te Velde; Sietse Mosselman; Peter L Pearson Journal: Am J Hum Genet Date: 2004-02-04 Impact factor: 11.025
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: 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