Lu Hui, Wu Peng-Fei, Zhang Wan, Xia Kun
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China; Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Mult Scler Relat Disord. 2020 Sep;44:102300. doi: 10.1016/j.msard.2020.102300. Epub 2020 Jun 12.
. Coffee consumption has been suggested to decrease the risk of multiple sclerosis (MS). In this study, we aim to investigate the causal effect of coffee consumption on risk of MS by Mendelian randomization (MR) approaches.
. Through a genome-wide association study including 375,833 participants from UK Biobank, we obtained single-nucleotide polymorphisms (SNPs) associated with habitual coffee consumption (P < 5 × 10). Summary-level data for MS were obtained from a meta-analysis, incorporating 14,802 subjects with MS and 26,703 healthy controls of European ancestry, which was conducted by the International Multiple Sclerosis Genetics Consortium. MR analyses were performed using inverse-variance-weighted method, weighted median estimator, and MR-Egger regression. Additional analyses were further performed using MR-Egger intercept and Cochran's Q statistic to verify the robustness of our findings.
. Nine coffee-associated SNPs were selected as instrumental variables. We failed to detect a causal effect of coffee consumption on MS risk (odds ratio, 1,00; 95% confidence interval, 0.98-1.01; P = 0.48). In the main MR analysis. Consistent results were yielded in sensitivity analyses using the weighted median and MR-Egger methods, and no horizontal pleiotropy (P = 0.49) was identified.
. Our MR results indicated that coffee consumption might not be causally associated with risk of MS occurrence. Further well-designed genetic-epidemiological studies investigating the effect of coffee intake on the disease course, such as relapse and progression, are warranted.
有人提出饮用咖啡可降低患多发性硬化症（MS）的风险。在本研究中，我们旨在通过孟德尔随机化（MR）方法研究饮用咖啡对MS风险的因果效应。
通过一项涵盖英国生物银行375833名参与者的全基因组关联研究，我们获得了与习惯性咖啡饮用相关的单核苷酸多态性（SNP）（P<5×10）。MS的汇总数据来自一项荟萃分析，该分析纳入了14802名患有MS的受试者和26703名欧洲血统的健康对照，由国际多发性硬化症遗传学联盟进行。使用逆方差加权法、加权中位数估计器和MR-Egger回归进行MR分析。进一步使用MR-Egger截距和 Cochr an Q统计量进行额外分析，以验证我们研究结果的稳健性。
九个与咖啡相关的SNP被选为工具变量。我们未能检测到饮用咖啡对MS风险的因果效应（优势比，1.00；95%置信区间，0.98-1.01；P=0.48）。在主要的MR分析中。使用加权中位数和MR-Egger方法的敏感性分析得出了一致的结果，并且未发现水平多效性（P=0.49）。
我们的MR结果表明，饮用咖啡可能与MS发病风险无因果关系。有必要开展进一步精心设计的遗传流行病学研究，以调查咖啡摄入量对疾病进程（如复发和进展）的影响。
