Aspirin Use and Risk of Alzheimer's Disease: A 2-Sample Mendelian Randomization Study
Pingjian Ding1, Maria P Gorenflo1,2, Xiaofeng Zhu3
1Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
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.
Insights
This Mendelian randomization study suggests aspirin use may reduce Alzheimer
Area of Science:
- Neuroscience and Genetics
- Pharmacogenomics and Alzheimer's Disease Research
Background:
- Observational studies present conflicting evidence on the link between aspirin use and Alzheimer's disease (AD) risk.
- Confounding factors and reverse causality complicate observational findings, necessitating robust causal inference methods.
Conclusions:
- Mendelian randomization analysis suggests a genetically determined protective effect of aspirin use against Alzheimer's disease (AD).
- The observed protective effect may be influenced by underlying factors such as coronary heart disease, blood pressure, and lipid profiles.
- Further research is warranted to elucidate the complex interplay between aspirin, cardiovascular health, and AD risk.
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