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目的 运用孟德尔随机化(MR)方法探讨睡眠特征与女性生殖内分泌疾病间的因果关系。方法 从全基因组关联分析数据中筛选单核苷酸多态性(SNP)作为暴露因素的工具变量，采用逆方差加权法、加权中位数法等统计方法评估6种睡眠特征(失眠、打鼾、白天小睡、白天嗜睡、睡眠呼吸暂停综合征、不宁腿综合征)与女性生殖内分泌疾病(异常子宫出血、经前期综合征、不孕症)的因果关系，使用多效性检验、异质性检验和留一法检验评估结果的稳健性；并进行反向MR分析，评估女性生殖内分泌疾病与睡眠特征的因果关系。结果 逆方差加权法和敏感性分析结果显示，白天小睡是经前期综合征的危险因素[OR=5.965,95%CI(1.428,24.915),P=0.014],异质性检验(P=0.214)、MR-Egger截距检验(P=0.476)、MR-PRESSO检验(P=0.259)提示结果分析稳健。反向MR分析结果显示经前期综合征不会导致白天小睡的发生(P=0.242)。结论 睡眠特征与女性生殖内分泌疾病存在一定的因果关联，但仍需要进一步的观察性研究或机制研究加以验证。
Abstract：Objectives:To explore the relationship between sleep traits and female reproductive endocrine diseases with Mendelian randomization analysis.Methods:Single nucleotide polymorphism(SNP) loci were screened from genome-wide association study data as instrumental variables in place of exposure. Statistical methods such as inverse variance weighting and weighted median method were used to assess the causal relationship between sleep traits(insomnia, snoring, daytime napping, daytime sleepiness, sleep apnoea, restless leg syndrome) and female reproductive endocrine diseases(abnormal uterine bleeding, premenstrual syndrome, infertility). The robustness of the assessment results was tested using the pleiotropy test, heterogeneity test and leave-one-out method. Also, reverse MR analysis was performed to assess the causal relationship between female reproductive endocrine diseases and sleep traits.Results:The results of inverse variance weighting method and sensitivity analysis showed that daytime napping was a risk factor of premenstrual syndrome [OR=5.965,95%CI(1.428,24.915),P=0.014]. The results of heterogeneity test(P=0.214),MR-Egger intercept test(P=0.476) and MR-PRESSO test(P=0.259) verified the robustness of result analysis. Reverse MR results showed premenstrual syndrome could not cause daytime napping(P=0.242).Conclusions:The study established some degree of causal association between sleep traits and female reproductive endocrine diseases, but further observational or mechanistic studies are needed to validate them.
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基本信息:
中图分类号:R711.7
引用信息:
[1]刘晓璐,董宏利.睡眠特征与女性生殖内分泌疾病因果关系的孟德尔随机化分析[J].生殖医学杂志,2025,34(11):1536-1544.
基金信息:
江苏省中医药管理局项目(YB2020056); 姑苏卫生重点人才项目(GSWS2020080); 苏州市卫生健康委员会科技项目(LCZX202321)
2025-11-15
2025-11-15