Circulating branched-chain amino acids and risk of psychiatric disorders: A two-sample Mendelian randomization study

Objective: Several studies have identified biomarkers that help in the prevention, diagnosis, and treatment of psychiatric disorders. The current study aimed to explore the association between circulating branched-chain amino acids (BCAA) and the risk of five psychiatric disorders. Methods: GWAS summary statistics were obtained from the UK Biobank and the FinnGen Biobank. The inverse variance weighted (IVW) method was used as a primary method to assess causal effects. The heterogeneity test, the horizontal pleiotropy test, and leave-one-out analysis were used to assess the robustness and reliability of the results. Results: Total BCAA levels were not significantly associated with the risk of anxiety disorders, alcohol dependence, depression, panic disorder, and bipolar affective disorders. Separate analyses for each BCAA showed that the levels of valine and leucine were not associated with the risk of the mentioned five psychiatric disorders, and the levels of isoleucine were not associated with the risk of depression, panic disorder, and bipolar affective disorders, but with the risk of anxiety disorders (IVW: OR = 0.814, 95 %CI = 0.716-0.925) and alcohol dependence (IVW: 0.690, 95 %CI = 0.560-0.849). Conclusions: Circulating isoleucine was a protective factor for anxiety disorders and alcohol dependence, offering a new research direction and theoretical basis for preventing and managing psychiatric disorders.