Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.

BACKGROUND & AIM: The association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD. METHODS: The instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancestry. Genetic association estimates for AAO of HD were obtained from the Genetic Modifiers of Huntington's Disease Consortium GWAS meta-analysis including 9064 HD patients of European ancestry. The inverse variance weighted method was used to evaluate the causal estimate and a comprehensive set of analyses tested the robustness of our results. RESULTS: Genetically predicted higher coffee consumption was associated with an earlier AAO of HD (ß = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias. CONCLUSIONS: This genetic study suggests high coffee consumption is associated with an earlier AAO of HD. Coffee is widely consumed and thus our findings, if confirmed, offers a potential way to delay the onset of this debilitating autosomal dominant disease.

Higher tea consumption is associated with decreased risk of small vessel stroke.

BACKGROUND & AIM: Observational studies have reported that tea consumption is associated with risk of stroke. However, this observed association is inconsistent, and whether this observed association is due to confounding factors or reverse causation remains unclear. Thus, we applied a two-sample mendelian randomization (MR) approach to determine whether genetically predicted tea consumption is causally associated with risk of stroke, ischemic stroke (IS), and IS subtypes. METHODS: UK Biobank available data (349,376 samples of European ancestry) was used to identify single nucleotide polymorphisms associated with tea consumption (cups/day). The summary statistics for stroke, IS, and IS subtypes were obtained from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls. RESULTS: We found that genetically predicted an extra daily cup of tea consumption was casually associated with a reduced risk of small vessel stroke (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69-0.91; P = 0.001), but not with cardioembolic stroke (OR, 0.97; 95% CI, 0.86-1.09; P = 0.582), large artery stroke (OR, 0.95; 95% CI, 0.82-1.10; P = 0.506), stroke (OR, 1.00; 95% CI, 0.95-1.06; P = 0.889) or IS (OR, 0.95; 95% CI, 0.89-1.01; P = 0.083). CONCLUSIONS: Our study provided evidence that genetically predicted an extra daily cup of tea consumption is causally associated with a reduced risk of small vessel stroke.