Objective: Studies have shown that age at natural menopause is heritable. Mutations in the FSH-receptor have been identified in women with premature ovarian failure (POF) and the FSH-receptor gene may, therefore, be considered a candidate gene for (early) menopausal age. This study investigates whether there is linkage between genetic markers in the FSH-receptor region and (early) age at menopause using a sib-pair design.
Design: Sib-pair based linkage analysis.
Setting: Sister pairs and their first-degree family members from The Netherlands.
Patient(s): The inclusion criteria for a family were natural menopause in upper or lower tail of the distribution of menopausal age in at least two sisters. A total of 126 families with at least one sib-pair were included in this study. Six polymorphic markers encompassing the FSH-receptor gene were genotyped.
Intervention(s): None.
Main outcome measure(s): Single point and multipoint logarithm of the odds (LOD) scores.
Result(s): None of the markers showed evidence in favor of linkage with overall age at natural menopause or early age at natural menopause.
Conclusion(s): Possibly, age at natural menopause in the more or less normal range is not part of the spectrum of phenotypes determined by mutations in the FSH-receptor gene. Alternatively, our results might be explained by genetic heterogeneity in the left tail of the distribution of menopausal age. This can limit the chance of finding a genetic locus, especially if this factor has a modest contribution to the phenotype.