Genes control the cessation of a woman's reproductive life: A twin study of hysterectomy and age at menopause
Genes control the cessation of a woman's reproductive life: A twin study of hysterectomy and age at menopause
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DOI：
10.1210/jc.83.6.1875
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发表时间：
1998-06-01
影响因子：
5.8
通讯作者：
Spector, TD
中科院分区：
文献类型：
--
作者：
Snieder, H;MacGregor, AJ;Spector, TD
一项经典的双胞胎研究被用来评估遗传因素在多大程度上解释了绝经年龄和子宫切除术（指征）的个体差异。进一步研究了遗传对绝经时间的影响是否通过遗传对初潮年龄的影响来介导。研究对象为275对同卵双生女性和353对异卵双生女性。最大似然模型拟合用于估计遗传和环境方差分量，Kaplan-Meier生存分析用于解释删失数据，考克斯比例风险模型用于调整潜在混杂因素。指定加性遗传和独特环境因素的模型显示出与数据的最佳拟合，绝经年龄的遗传率（h（2））为63%。遗传效应的显著性通过生存分析得到证实，并且不受混杂因素调整的影响。绝经早期和晚期都受到遗传因素的显著影响。子宫切除术也显示出相当大的遗传性（h（2）= 59%），其两个主要适应症：子宫肌瘤（h（2）= 69%）和月经过多（h（2）= 55%）也是如此。初潮年龄变异的遗传贡献估计为45%，其中大部分（37%）是由于显性遗传效应。绝经年龄和初潮年龄之间没有相关性，表明不同的遗传机制。这项研究为遗传因素在决定自然和手术绝经中的重要性提供了令人信服的证据。了解基因如何控制更年期的时间，并探索这些基因是否与疾病间接相关，是未来研究的重要领域。
A classical twin study was performed to assess the extent to which genetic factors explain individual differences in age at menopause and (indications for) hysterectomy. It was further examined whether a genetic effect on the timing of the menopause was mediated through a genetic effect on age at menarche. The subjects were 275 monozygotic and 353 dizygotic female twin pairs. Maximum likelihood model fitting was used to estimate genetic and environmental variance components, Kaplan-Meier survival analysis was used to account for censored data, and the Cox proportional hazards model was used to adjust for potential confounders. A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability (h(2)) for age at menopause of 63%. The significance of the genetic effect was confirmed by the survival analysis and was not affected by adjustment for confounders. Both early and late menopause were found to be significantly influenced by genetic factors. Hysterectomy also showed considerable heritability (h(2) = 59%), as did its two main indications: fibroids (h(2) = 69%) and menorrhagia (h(2) = 55%). The genetic contribution to the variance in age at menarche was estimated to be 45%, with the majority (37%) being due to dominant genetic effects. No correlation was found between age at menopause and age at menarche, suggesting different genetic mechanisms. This study provides convincing evidence for the importance of genetic factors in determining natural and surgical menopause. Understanding how genes control the timing of menopause and exploring whether these genes are indirectly associated with disease are important areas for future study.