Obesity causally influencing brain cortical structure: a Mendelian randomization study

Obesity may lead to cognitive impairment and psychiatric disorders, which are associated with alterations in the brain cortical structure. However, the exact causality remains inconclusive. We aimed to conduct two-sample Mendelian randomization (MR) analysis to identify the causal associations of obesity [body mass index (BMI), waist-hip ratio (WHR), and waist-hip ratio adjusted for BMI ((WHRadjBMI)) and brain cortical structure (cortical thickness and cortical surface area). Inverse-variance weighted (IVW) method was used as the main analysis, whereas a series of sensitivity analyses were employed to assess heterogeneity and pleiotropy. The main MR results showed that higher BMI significantly increased the cortical surface area of the transverse temporal (β = 5.13 mm2, 95% confidence interval [CI]: 2.55-7.71, P = 9.9 × 10-5); higher WHR significantly decreased cortical surface area of the inferior temporal (β = -38.60, 95% CI: -56.67- -20.54, P = 1.2 × 10-5), but significantly increased cortical surface area of the isthmus cingulate (β = 14.25, 95% CI: 6.97-21.54, P = 1.2 × 10-4). No significant evidence of pleiotropy was found in the MR analyses. This study supports that obesity has a causal effect on the brain cortical structure. Further studies are warranted to understand the clinical outcomes caused by these effects.