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

Abstract

Abstract Background 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. Methods 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. 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. Conclusions The evidence from our MR analyses suggests that there is no causal effect of childhood obesity on the risk of Alzheimer’s disease.

Keywords

• Childhood obesity
• Alzheimer's disease
• Dementia
• Mendelian randomization