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| 女性生殖行为与骨质疏松症的孟德尔随机化分析 |
| The mendelian randomization analysis of female reproductive behaviors and osteoporosis |
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| DOI：10.3969/j.issn.1006-7108.2025.12.010 |
| 中文关键词: 骨质疏松症 生殖行为 孟德尔随机化 因果关系 |
| 英文关键词:Osteoporosis reproductive behavior Mendelian randomization causal relationship |
| 基金项目:甘肃省自然科学基金（22JR5RA640，23JRRA1679，24JRRA582） |
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| 中文摘要: |
| 目的 采用两样本孟德尔随机化方法，探讨女性生殖行为与骨质疏松症（osteoporosis，OP）之间的因果关系，为女性OP的个性化预防和精准管理提供理论依据。方法 从大型公开可检索的基因组关联研究数据库中获取汇总数据，选择初潮年龄、绝经年龄、初次妊娠年龄及末次妊娠年龄作为暴露变量，OP为结局变量。利用单核苷酸多态性作为工具变量，应用逆方差加权法为主要分析方法，并结合Leave-one-out“留一法”敏感性分析，评估暴露因素对OP的潜在因果效应。结果 两样本孟德尔随机化分析显示，初潮年龄与OP风险呈正向关联［OR=1.08，95%CI（1.00，1.15），P=0.038］，绝经年龄与OP风险呈负向关联［OR=0.95，95%CI（0.92，0.98），P=0.001］；初次妊娠年龄及末次妊娠年龄与OP无显著因果关系（P＞0.05）。敏感性分析结果稳健。结论 初潮年龄较晚可能增加OP风险，绝经年龄较晚则具有保护作用，妊娠行为对OP的因果关系尚不显著。 |
| 英文摘要: |
| Objective To investigate the causal relationship between women's reproductive behaviors and osteoporosis using a two-sample Mendelian randomizationapproach, providing theoretical evidence for personalized prevention and precise management of osteoporosis in women. Methods Summary-level data were obtained from large, publicly accessible genome-wide association study datasets. Age at menarche, age at menopause, age at first pregnancy, and age at last pregnancy were selected as exposure variables, while osteoporosis was considered the outcome variable. Single nucleotide polymorphisms were used as instrumental variables. The inverse-variance weighted method served as the primary analytical approach, with leave-one-out sensitivity analysis employed to assess the robustness of the findings. Results Two-sample MR analysis indicated a positive association between age at menarche and osteoporosis risk (OR = 1.08, 95% CI: 1.00–1.15, P = 0.038), while age at menopause was negatively associated with osteoporosis risk (OR = 0.95, 95% CI: 0.92–0.98, P = 0.001). No significant causal relationships were identified between age at first pregnancy or age at last pregnancy and osteoporosis (P> 0.05). Sensitivity analyses confirmed the robustness of these findings. Conclusion A later age at menarche may increase the risk of osteoporosis, whereas a later age at menopause appears to have a protective effect. The causal relationships between pregnancy-related factors and osteoporosis remain inconclusive. |
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