Association between brain resting-state functional activities and obesity: A bidirectional Mendelian randomization study.

BACKGROUND

Investigations revealed significant changes in brain activity between people with obesity or overweight and people with normal weight. The causal relationship between body weight and brain functional activity remains unclear and warrants further investigation.

METHODS

We conducted a bidirectional two-sample Mendelian randomization (MR) study. We gathered summary statistics from genome-wide association studies for 191 resting-state functional magnetic resonance imaging phenotypes and obesity traits (body mass index, body fat percentage, waist-to-hip ratio). Inverse variance weighting, the weighted median, MR Egger, and the weighted mode were employed. We conducted pleiotropy and heterogeneity analyses to evaluate robustness and reliability.

RESULTS

Forward analysis revealed that the intensity of spontaneous brain activity in the calcarine, lingual, or cuneus gyri within the visual network (beta = -0.076; 95 % CI: -0.11 to -0.04; p = 6.97 × 10-5) had a causal effect on body weight. The reverse analysis revealed that body weight has a causal effect on the intensity of spontaneous brain activity in the precuneus, angular, and cingulate gyri (beta = 0.209; 95 % CI: 0.11 to 0.31; p = 2.41 × 10-5), and the angular and temporal gyri (beta = 0.215; 95 % CI: 0.11 to 0.32; p = 3.87 × 10-5) within the default mode and central executive network.

CONCLUSIONS

Genetic evidence proves a causal relationship between body weight and brain functional activity.