双向孟德尔随机化法对抑郁症与缺血性卒中间的因果关联研究

Bidirectional Mendelian Randomization Study on causal relationship between depression and ischemic stroke

目的本研究旨在探讨抑郁症与缺血性卒中之间的潜在因果关系,使用双向孟德尔随机化分析来评估这两种疾病是否存在双向因果关系,以提供更准确的预防和治疗策略。方法采用双向孟德尔随机化设计,分析大规模基因关联研究(GWAS)数据集,使用与抑郁症和缺血性卒中相关的单核苷酸多态性(SNPs)作为工具变量。遵循三个核心假设:IVs与暴露强相关、IVs与结局之间的关联仅通过暴露变量、不受结局的混杂因素影响。主要采用逆方差加权(IVW)方法,并利用MR-Egger回归、加权中位数和加权模式方法评估研究结果的可靠性及潜在的多效性。结果逆方差加权方法显示,抑郁症显著增加缺血性卒中的总体风险(OR=1.14,95%CI:1.05~1.24,P=0.001),特别是对大动脉粥样硬化性缺血性卒中的影响最为显著(OR=1.18,95%CI:1.08~1.29,P<0.001)。心源性缺血性卒中也显著增加了抑郁症的风险(OR=1.20,95%CI:1.11~1.30,P=0.0002)。异质性和敏感性分析支持了分析结果的稳健性。结论抑郁症显著增加了缺血性卒中的风险,特别是大动脉粥样硬化性卒中,而心源性缺血性卒中也显著增加了抑郁症的风险。

Objective This study aimed to explore the potential causal relationship between depression and ischemic stroke,employing Bidirectional Mendelian Randomization Analysis to assess if a causal relationship exists between these two conditions,and to provide more accurate strategies for prevention and treatment.Methods A Bidirectional Mendelian Randomization design was utilized,analyzing large-scale genome-wide association study(GWAS)datasets,with single nucleotide polymorphisms(SNPs)related to depression and ischemic stroke serving as instrumental variables.The study adhered to three core assumptions:IVs are strongly associated with exposure,the association between IVs and outcomes was solely through the exposure variable,and IVs were not influenced by confounders of the outcome.The primary method used was the inverse variance weighted(IVW)method,supplemented by MR-Egger regression,weighted median,and weighted mode methods to evaluate the reliability of the study results and potential pleiotropy.Results The inverse variance weighted method indicated that depression significantly increased the overall risk of ischemic stroke(OR=1.14,95%CI:1.05~1.24,P=0.001),especially the risk of large artery atherosclerotic stroke(OR=1.18,95%CI:1.08~1.29,P<0.001).Cardiogenic ischemic stroke also significantly increased the risk of depression(OR=1.20,95%CI:1.11~1.30,P=0.0002).Heterogeneity and sensitivity analysis supported the robustness of the findings.Conclusions Depression significantly increases the risk of ischemic stroke,particularly large artery atherosclerotic stroke,while cardiogenic ischemic stroke significantly increases the risk of depression.