Affiliations: [a]
Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| [b]
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA
| [c]
Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
Correspondence:
[*]
Correspondence to: Rong Xu, Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Tel.: +1 216 368 0023; E-mail: [email protected].
Abstract: Background:Observational studies have shown inconsistent findings of the relationships between aspirin use and the risk of Alzheimer’s disease (AD). Objective:Since residual confounding and reverse causality were challenging issues inherent in observational studies, we conducted a 2-sample Mendelian randomization analysis (MR) to investigate whether aspirin use was causally associated with the risk of AD. Methods:We conducted 2-sample MR analyses utilizing summary genetic association statistics to estimate the potential causal relationship between aspirin use and AD. Single-nucleotide variants associated with aspirin use in a genome-wide association study (GWAS) of UK Biobank were considered as genetic proxies for aspirin use. The GWAS summary-level data of AD were derived from a meta-analysis of GWAS data from the International Genomics of Alzheimer’s Project (IGAP) stage I. Results:Univariable MR analysis based on these two large GWAS data sources showed that genetically proxied aspirin use was associated with a decreased risk of AD (Odds Ratio (OR): 0.87; 95%CI: 0.77–0.99). In multivariate MR analyses, the causal estimates remained significant after adjusting for chronic pain, inflammation, heart failure (OR = 0.88, 95%CI = 0.78–0.98), or stroke (OR = 0.87, 95%CI = 0.77–0.99), but was attenuated when adjusting for coronary heart disease, blood pressure, and blood lipids. Conclusion:Findings from this MR analysis suggest a genetic protective effect of aspirin use on AD, possibly influenced by coronary heart disease, blood pressure, and lipid levels.
