The Causation Between Alcohol Consumption With Common Mental Disorders:A Two-Sample Mendelian Randomization Study

Background: Epidemiological and clinical observational studies have reported high comorbidity rates of alcohol use disorder（AUD）and mental diseases,suggesting that there is a close relationship between alcohol consumption and common mental diseases,but no study has reported the causal relationship between them.Two-Sample Mendelian Randomization（TSMR）analysis can remedy for the shortcomings of traditional observational research in eliminating confounding factors and clarifying causality,and provide a new idea for etiological exploration in epidemiological research.Objective: Based on the current published summary database of GWAS,the causal association between alcohol consumption and common mental diseases schizophrenia（SCZ）,major depressive disorder（MDD）and bipolar disorder（BD）is analyzed from the perspective of genetics by using TSRM analysis.Methods: Through the published GWAS database,the total scores of weekly alcohol consumption,alcohol dependence,alcohol use disorders identification test（AUDIT）and relevant GWAS data of SCZ,MDD and BD were obtained.According to the three core hypotheses required by Mendelian randomization,genetic instrumental variables（IVs）were selected.Inverse Variance Weighted（IVW）method,MR-Egger regression method and Weighted Median Estimator（WME）method were used for tsmr analysis.In order to ensure the accuracy and stability of the research results,heterogeneity test,multiple validity test and sensitivity analysis were conducted.Results:1.There was heterogeneity between weekly alcohol consumption,AUDIT overall score and SCZ related data,and there was horizontal pleiotropy between alcohol dependence and SCZ related data.Appropriate test methods were selected for correlation analysis.The results were as follows:（1）weekly alcohol consumption and SCZ [IVW method（random effect model）OR=1.01,95% CI:0.65-1.56,P=0.97];（2）Alcohol dependence and SCZ [IVW method（fixed effect model）OR=1.03,95%CI:0.97-1.08,P=0.36;MR-Egger regression method OR=0.81,95%CI:0.69-0.95,P=0.02;WME method OR=1.00,95%CI:0.92-1.09,P=0.99];（3）AUDIT overall score and SCZ [IVW method（random effect model）OR=1.11,95%CI:0.37-3.29,P=0.85].Sensitivity analysis did not find any SNP that had a significant impact on the robustness of the results.Therefore,the above results show that there is no clear causal relationship between drinking and SCZ.2.There was heterogeneity in the data associated with weekly alcohol consumption and MDD.Appropriate test methods were selected for correlation analysis,and the results were as follows:（1）weekly alcohol consumption and MDD [IVW method（random effect model）OR=1.11,95%CI: 0.91-1.36,P=0.31];（2）alcohol dependence and MDD[IVW method（fixed effect model）OR=1.01,95%CI: 0.98-1.06,P=0.46];（3）AUDIT overall score and MDD [IVW method（fixed effect model）OR=1.21,95%CI: 0.47-1.97,P=0.45].Sensitivity analysis did not find SNPs that had a significant impact on the robustness of the results.This finding pointed out that alcohol consumption had no effect on MDD.3.There was heterogeneity in the data related to weekly alcohol consumption and BD,and there was horizontal pleiotropy in the data related to alcohol dependence and BD.Appropriate test methods were selected for correlation analysis,and the results were as follows:（1）weekly alcohol consumption and BD [IVW method（random effect model）OR = 0.90,95% CI: 0.52-1.51,P = 0.67];（2）alcohol dependence and BD[IVW method（fixed effect model）OR = 1.00,95%CI: 0.93-1.07,P =0.94);MR-Egger regression OR = 0.76,95% CI: 0.63-0.93,P = 0.02;WME method OR = 0.99,95% CI: 0.90-1.10,P = 0.89];（3）AUDIT overall score and BD [IVW method（fixed effect model）OR = 0.68,95%CI: 0.32-1.45,P = 0.32].Sensitivity analysis did not find SNPs that had a significant impact on the robustness of the results.The above results supported that there was no causal relationship between alcohol consumption and BD.Conclusion: Based on the GWAS database,this study which utilized TSMR analysis found no explicit causal relationship between drinking and common mental diseases SCZ,MDD and BD from the perspective of genetics.