Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.
Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.
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DOI：
10.1016/j.clnu.2021.09.041
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发表时间：
2021-11
影响因子：
6.3
通讯作者：
Lian, Xuegan
中科院分区：
文献类型：
--
作者：
Wang, Mengmeng;Cornelis, Marilyn C.;Zhang, Zhizhong;Liu, Dandan;Lian, Xuegan
习惯性咖啡或咖啡因摄入与亨廷顿病（HD）发病年龄（AAO）之间的关系尚不清楚。我们采用孟德尔随机化法来研究咖啡摄入量与HD的AAO之间的因果关系。我们从对375，833名欧洲血统个体的全基因组关联研究（GWAS）荟萃分析中选择了14种与咖啡消费相关的独立遗传变异。HD的AAO的遗传关联估计值来自亨廷顿病遗传修饰剂联合会GWAS荟萃分析，包括9，064例欧洲血统的HD患者。使用逆方差加权法来评估因果估计，并进行了一系列全面的分析，测试了我们的结果的稳健性。遗传学预测的较高咖啡消费量与HD的早期AAO相关（β =-1.84岁，95%置信区间（CI）=-3.47至0.22，P = 0.026）。结果对潜在多效性和弱仪器偏倚具有稳健性。这项遗传研究表明，高咖啡消费与HD的早期AAO有关。咖啡被广泛消费，因此我们的研究结果，如果得到证实，提供了一种潜在的方法来延迟这种使人衰弱的常染色体显性疾病的发作。
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. We selected 14 independent genetic variants associated with coffee consumption 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 9,064 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 (CI) = −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.
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