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Genetically Predicted Coffee Consumption and Risk of Alzheimer's Disease and Stroke.

BACKGROUND
Observational studies have reported that coffee consumption was associated with Alzheimer's disease (AD) and stroke risk. However, the results are inconclusive.


OBJECTIVE
We aimed to evaluate whether genetically predicted coffee consumption is associated with AD and stroke using Mendelian randomization (MR) design.


METHODS
Summary-level data for AD (n = 54,162), ischemic stroke (n = 440,328), and intracerebral hemorrhage (ICH, n = 3,026) was adopted from publicly available databases. Summary-level data for coffee consumption were obtained from two genome-wide association studies, comprising up to 375,833 subjects.


RESULTS
Genetically predicted coffee consumption (cups/day) was associated with an increased risk of AD (OR = 1.26, 95%CI = 1.05-1.51). Moreover, genetically predicted 50%increase of coffee consumption was associated with an increased risk of ICH (OR: 2.27, 95%CI: 1.08-4.78) but a decreased risk of small vessel stroke (OR: 0.71, 95%CI: 0.51-0.996). Estimate for AD and ICH in FinnGen consortium is directionally consistent. Combined analysis of different databases further confirmed that genetically predicted coffee consumption was associated with an increased risk of AD and ICH. In the multivariable MR analysis, genetically predicted coffee consumption retained a stable effect with AD and ICH when adjusting for smoking (p <  0.05), while the association with AD attenuated when adjusting for alcohol use.


CONCLUSION
Our results indicate that genetically predicted coffee consumption may be associated with an increased risk of AD and ICH. The underlying biological mechanisms warrant further study.