1. Aspirin Use and Risk of Alzheimer's Disease: A 2-Sample Mendelian Randomization Study.
- Author
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Ding, Pingjian, Gorenflo, Maria P., Zhu, Xiaofeng, and Xu, Rong
- Subjects
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DISEASE risk factors , *ASPIRIN , *ALZHEIMER'S disease , *GENOME-wide association studies , *CORONARY disease - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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