Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis

Abstract

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy.

Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study.

Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38).

Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.

Keywords: BMI; alcohol consumer; alcohol intake frequency; fat percentage; major depression (MDD).

Figure 1

MR results for the relationship between alcohol and major depression. (A) forest plot of individual and combined SNP MR-estimated effect sizes. The effect estimates represent the log odds for major depression increase in alcohol consumption, and the error bars represent 95% CIs. (B) Scatter plot of SNP effects on relative alcohol consumption vs. major depression, with the slope of each line corresponding to the estimated MR effect per method. The data are expressed as raw β values with 95% CIs. (C) Forest plot of individual and combined SNP MR-estimated effect sizes, that is alcohol intake frequency and major depression. (D) Scatter plot of SNP effects on relative alcohol intake frequency vs. major depression.

Figure 2

Two-step MR analysis framework. Step 1 estimated the causal effect of the exposure on the potential mediators, and step 2 assessed the causal effect of the mediators on major depression. “Direct effect” indicates the effect of exposure on major depression. “Indirect effect” indicates the effect of exposure on major depression through the mediator. IVs, instrumental variables.