Causality of genetically determined metabolites on anxiety disorders: a two-sample Mendelian randomization study

作者：Gui Xiao, Qingnan He, Li Liu, Tingting Zhang, Mengjia Zhou, Xingxing Li, Yijun Chen, Yanyi Chen, Chunxiang Qin · 发表于：Journal of Translational Medicine · 年份：2022 · DOI：10.1186/s12967-022-03691-2 · 被引用次数：149 · 研究领域：Genetic Associations and Epidemiology、Bioinformatics and Genomic Networks、Metabolomics and Mass Spectrometry Studies

Abstract Background Although anxiety disorders are one of the most prevalent mental disorders, their underlying biological mechanisms have not yet been fully elucidated. In recent years, genetically determined metabolites (GDMs) have been used to reveal the biological mechanisms of mental disorders. However, this strategy has not been applied to anxiety disorders. Herein, we explored the causality of GDMs on anxiety disorders through Mendelian randomization study, with the overarching goal of unraveling the biological mechanisms. Methods A two-sample Mendelian randomization (MR) analysis was implemented to assess the causality of GDMs on anxiety disorders. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas four different GWAS datasets of anxiety disorders were the outcomes. Notably, all datasets were acquired from publicly available databases. A genetic instrumental variable (IV) was used to explore the causality between the metabolite and anxiety disorders for each metabolite. The MR Steiger filtering method was implemented to examine the causality between metabolites and anxiety disorders. The standard inverse variance weighted (IVW) method was first used for the causality analysis, followed by three additional MR methods (the MR-Egger, weighted median, and MR-PRESSO (pleiotropy residual sum and outlier) methods) for sensitivity analyses in MR analysis. MR-Egger intercept, and Cochran’s Q statistical analysis were used to evaluate po...