Unveiling the causal relationships between circulating metabolites and intelligence: A bidirectional Mendelian randomization study

Observational studies suggest a link between circulating metabolites and intelligence. Nevertheless, the causal association between circulating metabolites and intelligence has not been elucidated. Thus, we performed a 2-sample MR study to assess the influence of circulating metabolites on intelligence. The causal relationships between circulating metabolites and intelligence are determined by using a bidirectional MR analysis. We drew on summary statistics from the circulating metabolites (19,273 individuals) and intelligence (2,69,867 individuals) genome-wide association study on individuals of European ancestry. To estimate a causal effect, we conducted inverse variance weighted, Egger regression (MR-Egger), weighted median, weighted model, and simple mode for the MR analysis. We carried out heterogeneity test, pleiotropy test, and "leave-one-out" approach for the sensitivity analysis to confirm the stability and robustness. The omega-6 fatty acids had protective causal effects on intelligence (OR: 1.019, 95% CI: 1.000-1.038, P = .048), while glycoprotein acetyls (OR: 0.955, 95% CI: 0.918-0.994, P = .024), concentration of vary large VLDL particles (OR: 0.960, 95% CI: 0.937-0.984, P = .001), triglycerides in small HDL (OR: 0.963, 95% CI: 0.936-0.991, P = .011), tyrosine (OR: 0.927, 95% CI: 0.886-0.971, P = .001), mean diameter for VLDL particles (OR: 0.976, 95% CI: 0.957-0.995, P = .015) had an anti-protective effect on intelligence. Reversed MR showed causal effects of intelligence on omega-6 fatty acids (OR: 0.886, 95% CI: 0.791-0.992, P = .036). Our MR findings yielded suggestive evidence supporting the causal association between specific metabolites and intelligence, necessitating further studies to explore the biological mechanism by which these metabolites might affect the development of intelligence.