Circulating metabolites and depression: a bidirectional Mendelian randomization

• Published in: Frontiers in neuroscience Vol. 17; p. 1146613
• Main Authors: Dong, Yankai, Zou, Zengxiao, Deng, Pin, Fan, Xiaoping, Li, Chunlin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 21.04.2023; Frontiers Media S.A
• Subjects: Apolipoprotein A; bidirectional; Cardiovascular disease; circulating metabolites; Confounding (Statistics); depression; Genome-wide association studies; Genomes; Glutamine; Glycoproteins; instrumental variable; Isoleucine; Mendelian randomization; Mental depression; Meta-analysis; Metabolism; Metabolites; Neuroscience; Pleiotropy; Risk factors; Software; Statistical analysis; Statistics; Netherlands; Finland; bidirectional; instrumental variable; Mendelian randomization; depression; circulating metabolites
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2023.1146613

Studies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression. In this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites ( = 24,925) and depression ( = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and "leave-one-out" methods. Apolipoprotein A-I (OR 0.990, 95% CI 981-0.999) and glutamine (OR 0.985, 95% CI 0.972-0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009-1.034), glycoproteins (OR 1.005, 95% CI 1.000-1.009), isoleucine (OR 1.013, 95% CI 1.002-1.024), and urea (OR 1.020, 95% CI 1.000-1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites. In this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.