精神疾病与酒精饮用的因果关联:两样本孟德尔随机化分析

Evidence of Causal Effect of Alcohol Use on Mental Disorders:a 2-Sample Mendelian Randomization Study

科学研究表明精神疾病与饮酒具有较强的关联性,但这种关联的具体影响仍未被清楚地揭示。为了促进公共卫生的发展和临床干预治疗的进行,我们试图探讨精神疾病与饮酒的因果关系。基于全基因组关联性研究的最新公开统计数据,我们进行了两样本孟德尔随机化分析。研究对象涉及5种主要精神障碍(重度抑郁症,双相情感障碍,精神分裂症,自闭症谱系障碍,注意力缺陷多动障碍)以及酒精饮用(酒精依赖,酒精问题和每天饮酒次数)。主要分析方法为逆方差加权、MR-Egger回归分析、加权中位数分析以及MR-PRESSO,被进一步用作敏感性分析。我们发现了精神分裂症与酒精依赖(IVW beta=0.1585,95%CI在0.0584~0.2587,P=0.0019)和每天饮酒次数(IVW beta=-0.01314,95%CI在-0.02187~-0.004417,P=0.0032)之间存在因果关联。另外,自闭症谱系障碍(IVW beta=0.4259,95%CI在-0.7848~-0.06705,P=0.020)和注意力缺陷多动障碍(IVW beta=0.2257,95%CI在0.02383~0.4275,P=0.028)对酒精依赖也存在潜在的因果关联。我们的结果表明了精神分裂症和注意力缺陷多动障碍会增加酒精依赖的风险,同时也揭示精神分裂症与酒精饮用之间的因果关系,以及从自闭症谱系障碍和注意力缺陷多动障碍对于酒精使用的潜在因果关系。

Several mental disorders have consistently been found high likelihood to co-occur with alcohol use,but the nature of such association is still an unresolved issue.To facilitate public health and the intervention procedure for clinical treatment,the main question we are trying to answer is whether there is a causal effect of alcohol use on mental disease.We applied two-sample Mendelian randomization(MR)analysis,using the newest publicly available summary statistics from genome-wide association studies(GWAS)on five major mental disorders,including major depressive disorders(MDD),bipolar disorders(BPD),schizophrenia(SCZ),autism spectrum disorder(ASD),attention-deficit hyperactivity disorder(ADHD)and alcohol use(alcohol dependence,alcohol problems,and drinks per day).The analyzing method was inverse-variance weighted(IVW).MR-Egger regression and weighted median(WM)analyses were further used as sensitivity analyses.We found evidence for significant causal effects of SCZ on alcohol dependence(IVW beta=0.1585,95%CI,0.0584 to 0.2587,P=0.0019),and on drinks per day(IVW beta=-0.01314,95%CI,-0.02187 to-0.004417,P=0.0032).We also found suggestive causal evidence for ASD(IVW beta=0.4259,95%CI-0.7848 to-0.06705,P=0.020)on alcohol dependence and ADHD(IVW beta=0.2257,95%CI 0.02383 to 0.4275,P=0.028)on alcohol dependence.Our findings strongly suggested SCZ and ADHD would increase the risk of alcohol dependence.Besides,the study also unraveled the causal relationships from SCZ to alcohol use and tentatively from ASD and ADHD to alcohol use.