Coffee Consumption and Risk of Stroke: A Mendelian Randomization Study

Objective Observational epidemiological studies have reported a relationship between coffee intake and risk of stroke. However, evidence for this association is inconsistent, and it remains uncertain whether the association is causal or due to confounding or reverse causality. To clarify this relationship, we adopted a Mendelian randomization (MR) approach to evaluate the effects of coffee consumption on the risk of stroke and its subtypes. Methods A meta‐analysis of genome‐wide association studies (GWASs) including 91,462 coffee consumers was used to identify instruments for coffee consumption. Summary‐level data for stroke, intracerebral hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta‐analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse‐variance‐weighted, weighted‐median, MR‐PRESSO (Pleiotropy RESidual Sum and Outlier) test and MR‐Egger regression. Sensitivity analyses were further performed using alternative instruments to test the robustness of our findings. Results Genetically predicted coffee consumption (high vs infrequent/no) was not associated with risk of stroke. Similarly, among coffee consumers, MR analysis did not indicate causal associations between coffee consumption (cups/day) and risk of stroke. However, in the subgroup analysis, we found weak suggestive evidence for a potential protective effect of coffee consumption on risk of small vessel (SV)‐IS, although the association did not reach statistical significance after correction for multiple comparisons. Interpretation This study suggests that coffee consumption is not causally associated with risk of stroke or its subtypes. Further studies are warranted to elucidate the possible association between coffee intake and risk of SV‐IS, as well as its potential underlying mechanisms. ANN NEUROL 2020;87:525–532