Abstract
BACKGROUND: Socioeconomic status (SES) is considered to be associated with the prevalence of Alzheimer's disease (AD). However, the causal association remain unclear. Here, we determining whether income has a causal protective effect on the risk of developing AD using Mendelian randomization (MR). METHODS: Single-nucleotide polymorphisms (SNPs) that are strongly associated with household income levels (P<5×10(-8)) from the UK Biobank (UKB) (n=286,301) were selected as instrumental variables for this study. Confounding instruments were removed through data set browsing. Selected SNPs were then harmonized with results from an AD genome-wide meta-analysis (71,880 cases, 383,378 controls) including both case-control and proxy cases. The analysis was conducted using MR methods, and multiple sensitivity analyses were applied for testing of potential bias. RESULTS: After confounding instrument removal and clumping, 9 SNPs associated with household income level identified by the UKB were left for the MR analysis. Our results demonstrated that higher household income level was causally related with a lower risk of AD (odds ratio 0.78, 95% confidence interval: 0.69-0.89; P<0.001). Multiple sensitivity analyses suggested no obvious evidence for heterogeneity or pleiotropy of the results. CONCLUSIONS: Under MR assumptions, our results suggest robust evidence of a causal association between household income and AD risk, which may provide potential prevention strategies for this devastating disease.