Coffee Consumption and Risk of Stroke: A Mendelian Randomization Study

Area of Science:

• Epidemiology
• Genetics
• Neurology

Background:

• Observational studies suggest a link between coffee intake and stroke risk, but findings are inconsistent.
• Uncertainty exists regarding causality, confounding factors, and reverse causality in the coffee-stroke association.
• Mendelian randomization (MR) offers a robust approach to investigate causal relationships.

Purpose of the Study:

• To evaluate the causal effect of coffee consumption on the risk of stroke and its subtypes using MR.
• To clarify the inconsistent findings from previous observational studies on coffee intake and stroke.

Main Methods:

• Utilized a meta-analysis of genome-wide association studies (GWASs) for coffee consumption instruments (N=91,462).
• Obtained summary-level data for stroke and its subtypes from the MEGASTROKE consortium.
• Performed MR analyses with multiple methods (IVW, weighted-median, MR-PRESSO, MR-Egger) and sensitivity analyses.

Main Results:

• Genetically predicted high coffee consumption was not associated with overall stroke risk.
• MR analysis showed no causal association between coffee consumption (cups/day) and stroke risk.
• Weak suggestive evidence indicated a potential protective effect of coffee on small vessel ischemic stroke (SV-IS), but not statistically significant.

Conclusions:

• Coffee consumption is not causally associated with the risk of stroke or its major subtypes.
• Further investigation is warranted for the potential association between coffee intake and SV-IS risk.
• Additional research is needed to understand the underlying mechanisms for any observed SV-IS association.