Causal Relationship Between Basal Metabolic Rate and Alzheimer’s Disease: A Bidirectional Two-sample Mendelian Randomization Study

Abstract Introduction Objective observational studies have shown that basal metabolic rate (BMR) decreases in patients with Alzheimer’s disease (AD), but the causal relationship between BMR and AD has not been established. We determined the causal relationship between BMR and AD by two-way Mendelian randomization (MR) and investigated the impact of factors associated with BMR on AD. Methods We obtained BMR (n = 454,874) and AD from a large genome-wide association study (GWAS) database (21,982 patients with AD, 41,944 controls). The causal relationship between AD and BMR was investigated using two-way MR. Additionally, we identified the causal relationship between AD and factors related with BMR, hyperthyroidism (hy/thy) and type 2 diabetes (T2D), height and weight. Results BMR had a causal relationship with AD [451 single nucleotide polymorphisms (SNPs), odds ratio (OR) 0.749, 95% confidence intervals (CIs) 0.663–0.858, P = 2.40E-03]. There was no causal relationship between hy/thy or T2D and AD (P > 0.05). The bidirectional MR showed that there was also a causal relationship between AD and BMR (OR 0.992, Cls 0.987–0.997, N SNPs18, P = 1.50E−03). BMR, height and weight have a protective effect on AD. Based on MVMR analysis, we found that genetically determined height and weight may be adjusted by BMR to have a causal effect on AD, not height and weight themselves. Conclusion Our study showed that higher BMR reduced the risk of AD, and patients with AD had a lower BMR. Because of a positive correlation with BMR, height and weight may have a protective effect on AD. The two metabolism-related diseases, hy/thy and T2D, had no causal relationship with AD.