Childhood obesity and risk of Alzheimer's disease: a Mendelian randomization study.

Abstract

Midlife obesity is a modifiable risk factor for Alzheimer's disease. However, the association between childhood obesity and Alzheimer's disease remains largely unknown. Therefore, we conducted a mendelian randomization analysis (MR) to assess the causal link between childhood obesity and Alzheimer's disease. Using summary statistics from publicly available genome-wide association studies (GWAS) database, we explored the genetic link between childhood obesity and Alzheimer's disease through a two-sample MR. The primary analysis employed the inverse-variance weighted (IVW) method. To complement our findings, we also employed MR-Egger, weighted median, simple model, and weighted model methods for MR estimates. Furthermore, we conducted Cochrane's Q-statistic test, Egger intercept test, and a leave-one-out sensitivity test to ensure the robustness and reliability of our results. The IVW analysis yielded non-significant results, indicating no significant genetic association between childhood obesity and Alzheimer's disease (OR = 0.958, 95% CI = 0.910-1.008, p = 0.095). Consistent with this, the results from MR-Egger, the weighted median, simple model, and weighted model approaches all supported these findings. Furthermore, we did not detect any signs of heterogeneity or pleiotropy, and our leave-one-out analysis confirmed that no single nucleotide polymorphisms had a substantial impact on the reliability of our results. The evidence from our MR analyses suggests that there is no causal effect of childhood obesity on the risk of Alzheimer's disease.