Systematic identification of risk factors and drug repurposing options for Alzheimer's disease

Abstract

Abstract Introduction Several Mendelian randomization studies have been conducted that identified multiple risk factors for Alzheimer's disease (AD). However, they typically focus on a few pre‐selected risk factors. Methods A two‐sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1037 risk factors/medical conditions and 31 drugs with the risk of late‐onset AD. To correct for multiple comparisons, the false discovery rate was set at < 0.05. Results There was strong evidence of a causal association between glioma risk, reduced trunk fat‐free mass, lower education levels, lower intelligence and a higher risk of AD. For 31 investigated treatments (such as antihypertensive drugs), we found limited evidence for their associations. Discussion MR found robust evidence of causal associations between glioma, trunk fat‐free, and AD. Our study also confirms that higher educational attainment and higher intelligence are associated with a reduced risk of AD.

Keywords

• Alzheimer's disease
• drug repurposing
• risk factors
• two‐sample Mendelian randomization