【摘要】 目的 通过孟德尔随机化(Mendelian randomization,MR)方法去除混杂因素和反向因果偏倚，以确定微量元素与双相情感障碍(bipolar disorder,BD)的确切因果关系。方法 基于公开的摘要级遗传统计数据，本研究采用双向双样本MR分析，以评估包括铜、钙、胡萝卜素、叶酸、铁、镁、钾、硒、维生素A、维生素B12、维生素B6、维生素C、维生素D、维生素E和锌在内的15种微量元素与BD的潜在因果关联。运用贝叶斯加权MR验证关联的可靠性，并通过敏感性分析评估异质性和水平多效性的影响。此外，在多变量MR分析中，以逆方差加权法为主要方法，纳入可能影响结局的混杂变量，以确定相关微量元素对BD因果作用的独立因果效应。结果 胡萝卜素(OR=1.227,95%CI:1.064～1.414)与维生素B12(OR=1.255,95%CI:1.090～1.445)对BD的因果影响在贝叶斯加权MR方法中的得到验证，提示可能具有统计学意义的相关性。同时，这些关联不太可能受到异质性和水平多效性的影响(P>0.05)。此外，其余13种微量元素未显示与BD有显著的因果关联。在随后的多变量MR分析中，调整潜在的混杂因素后，维生素B12(OR=1.366,95%CI:1.105～1.687)对BD的因果效应仍存在显著统计学意义，且通过Bonferroni校正。结论 本研究表明特定的微量元素尤其是胡萝卜素与维生素B12，可能在BD的发展中具有调节作用，这一发现为BD的预防和治疗策略提供了新的潜在靶点。更多还原

【Abstract】 Objective To determine the causal relationship between trace elements and bipolar disorder(BD) by employing Mendelian randomization(MR) methods to eliminate confounding factors and reverse causation bias.Methods Utilizing publicly available summary-level genetic statistical data,we conducted a bidirectional two-sample MR analysis to assess the po-tential causal associations between 15 trace elements,including copper,calcium,carotene,folate,iron,magnesium,potassium,selenium,vitamin A,vitamin B12,vitamin B6,vitamin C,vitamin D,vitamin E,and zinc,and BD.The reliability of the associations was verified using Bayesian weighted MR,and sensitivity analyses were performed to evaluate the effects of heterogeneity and horizontal pleiotropy.Additionally,in the multivariable MR analysis,inverse variance weighting was employed as the primary method,incorporating potential confounding variables that may affect the outcomes to determine the independent causal effects of the relevant trace elements on BD.Results The causal impacts of carotene(OR=1.227,95%CI:1.064-1.414) and vitamin B12(OR=1.255,95%CI:1.090-1.445) on BD were validated through the Bayesian weighted MR method,suggesting statistically significant correlations.Furthermore,these associations were unlikely to be influenced by heterogeneity and horizontal pleiotropy(P>0.05).In addition,the remaining 13 trace elements did not show significant causal associations with BD.In the subsequent multivariable MR analysis,after adjusting for potential confounding factors,the causal effect of vitamin B12(OR =1.366,95% CI:1.105-1.687) on BD remained statistically significant,even after Bonferroni correction.Conclusion This study indicates that specific trace elements,particularly carotene and vitamin B12,may play a modulatory role in the development of BD,providing new potential targets for the prevention and treatment strategies of BD.更多还原