Department of Neurology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Clin Nutr. 2021 Nov;40(11):5615-5618. doi: 10.1016/j.clnu.2021.09.041. Epub 2021 Oct 1.
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.
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.
Genetically predicted higher coffee consumption was associated with an earlier AAO of HD (β = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias.
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.
习惯性饮用咖啡或咖啡因与亨廷顿病（HD）发病年龄（AAO）的关系尚不清楚。我们采用孟德尔随机化方法来探究咖啡摄入与 HD 的 AAO 之间的因果关系。
从欧洲血统的 375833 人的全基因组关联研究（GWAS）荟萃分析中选择了 14 个与咖啡消费相关的独立遗传变异作为工具变量。HD 发病年龄的遗传关联估计值来自包括 9064 名欧洲血统的 HD 患者的亨廷顿病遗传修饰物联盟 GWAS 荟萃分析。采用逆方差加权法评估因果估计值，综合分析检验了结果的稳健性。
遗传预测的较高咖啡摄入量与较早的 HD AAO 相关（β = -1.84 岁，95%置信区间为-3.47 至-0.22，P = 0.026）。结果对于潜在的多效性和弱工具偏倚具有稳健性。
这项遗传研究表明，大量饮用咖啡与 HD 的 AAO 较早有关。咖啡的广泛消费，如果得到证实，为我们提供了一种潜在的方法，可以延缓这种使人衰弱的常染色体显性疾病的发病。
