The causality of physical activity status and intelligence: A bidirectional Mendelian randomization study

BACKGROUND: Observational studies suggest physical activity (PA) enhances intelligence, while sedentary behavior (SB) poses a risk. However, causality remains unclear. METHODS: We extracted genetic instruments from large genome-wide association studies summary data and employed an inverse-variance weighted (IVW) approach within a random-effects model as the primary method of Mendelian randomization (MR) analysis to estimate the overall effect of various physical activity statuses on intelligence. To assess IVW stability and MR sensitivity, we also utilized supplementary methods including weighted median, MR-Egger, and MR-PRESSO. Furthermore, multivariable MR analysis was conducted to examine the independent effects of each physical activity trait on intelligence. RESULTS: The MR primary results indicated that LST was negatively associated with intelligence (β = -0.133, 95%CI: -0.177 to -0.090, p = 1.34×10–9), while SBW (β = 0.261, 95% CI: 0.059 to 0.463, p = 0.011) may have a positive effect on intelligence; however, MVPA and SC did not show significant effects on intelligence. Inverse causality analyses demonstrated intelligence significantly influenced all physical activity states. CONCLUSIONS: Our study highlights a bidirectional causal relationship between physical activity states and intelligence.