双向两样本孟德尔随机化分析轻中度抑郁与膝骨性关节炎风险的关系

A bidirectional two-sample mendelian randomization analysis of the relationship between mild to moderate depression and the risk of knee osteoarthritis

目的 采用双向两样本孟德尔随机化(Mendelian randomization, MR)方法分析轻中度抑郁与膝骨性关节炎(knee osteoarthritis, KOA)之间的因果关系,为KOA的预防、治疗及预后评估提供新的思路。方法 利用全基因组关联研究(genome-wide association study, GWAS)数据进行分析,选择与轻中度抑郁密切相关的遗传位点、KOA密切相关的遗传位点分别作为工具变量,以逆方差加权(inverse variance weighted, IVW)法为评估因果效应的主要分析方法,以加权中位数(weighted median, WM)法、简单中位数(simple median, SM)法、加权中值(weighted mode)法和MR-Egger回归为辅,对数据进行双向两样本MR分析。采用OR值评价轻中度抑郁与KOA之间的因果关系,采用异质性检验、基因多效性检验和敏感性分析评估结果的稳定性和可靠性。结果 双向两样本MR分析表明轻中度抑郁患者患KOA的风险是健康人群的1.64倍(OR=1.64, 95%CI:1.34~2.02,P<0.001)。外部验证发现轻中度抑郁会导致KOA的风险增加,但反向双向两样本MR分析未能证明轻中度抑郁和KOA之间的因果效应。结论 轻中度抑郁与KOA之间可能存在因果关联,轻中度抑郁可能为KOA的危险因素。

Objective To utilize a bidirectional Mendelian randomization(MR)analysis to examine the causal link between mild-to-moderate depression and knee osteoarthritis(KOA),offering novel perspectives for the prevention,management,and prognostic evaluation of KOA.Methods Genome-wide association study(GWAS)data were utilized,genetic loci closely associated with mild-to-moderate depression and KOA were selected as instrumental variables.The inverse variance weighted(IVW)was employed as the primary analytical approach to assess causal effects,supplemented by methods such as weighted median(WM),simple median(SM),weighted mode,and MR-Egger regression for two-sample MR analysis.The causal relationship between mild-to-moderate depression and KOA was evaluated using OR,with tests for heterogeneity,genetic pleiotropy,and sensitivity analysis to assess the stability and reliability of the results.Results MR analysis indicated that patients with mild-to-moderate depression had a 1.64-fold increased risk of KOA compared to the healthy population(OR=1.64,95%CI:1.34-2.02;P<0.001).External validation confirmed that mild-to-moderate depression indeed increases the risk of KOA.Conclusions A potential causal association may exist between mild-to-moderate depression and KOA,with mild-to-moderate depression possibly serving as a risk factor for KOA.