TY - JOUR
T1 - Age at natural menopause is not linked with the follicle-stimulating hormone receptor region: a sib-pair study
AU - Kok, Helen S.
AU - van Asselt, Kristel M.
AU - Peeters, Petra H. M.
AU - van der Schouw, Yvonne T.
AU - Grobbee, Diederick E.
AU - Pearson, Peter L.
AU - Wijmenga, Cisca
PY - 2004
Y1 - 2004
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.fertnstert.2003.08.017
DO - https://doi.org/10.1016/j.fertnstert.2003.08.017
M3 - Article
C2 - 15037410
SN - 0015-0282
VL - 81
SP - 611
EP - 616
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 3
ER -