酒精依赖和肌萎缩侧索硬化因果关系的孟德尔随机化分析

Evaluating the Causal Relationship between Alcohol Dependence and Amyotrophic Lateral Sclerosis Using Mendelian Randomisation

目的采用孟德尔随机化方法探索饮酒行为和肌萎缩侧索硬化发病风险的因果关系。方法利用大样本全基因组关联研究数据,确定与酒精依赖密切相关的遗传位点作为工具变量,通过逆方差加权法、MR-Egger回归法等两样本孟德尔随机化方法,以比值比(OR值)作为结局指标对因果关系进行评价。结果本研究共纳入476例男性酒精依赖患者和1358例男性对照,IVW方法估计的OR值为1.12(95%可信区间:1.02-1.24,P=0.021),MR-Egger回归结果表明遗传多效性不会对结果造成偏倚(截距=-0.036,P=0.755)。结论本研究采用两样本孟德尔随机化的方法,表明在男性中严重的酒精依赖会增加肌萎缩侧索硬化的风险。

Objective To explore the causal relationship between alcohol dependence and the risk of amyotrophic lateral sclerosis using the Mendelian randomization(MR)analysis. Methods Genetic variants which are closely related to alcohol dependence in large sample GWAS were employed as instrumental variables;two-sample MR methods including IVW and MR-Egger regression was carried out to estimate the causal effect and to evaluate the possible pleotropic effects of instruments. Results A total of 476 male patients with alcohol dependence and 1,358 male controls were included in this study.The odd ratio between alcohol dependence and ALS was estimated to be 1.12(95% CI :1.02-1.24, P =0.021),and the MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results(the intercept=-0.036, P =0.755). Conclusion The results of the two-sample MR analysis provides the evidence that severe alcohol dependence can increase the risk of ALS.