Estimating the Causal Effect of Alcohol Consumption on Military-Relevant Mental Health Conditions: A Mendelian Randomization Study Using the All of Us Research Program.

INTRODUCTION: Depression, anxiety, and post-traumatic stress disorder (PTSD) are common, militarily relevant mental health disorders that severely impact operational readiness and can disqualify service members from flying class and special duty positions. While observational studies frequently correlate heavy alcohol consumption with these conditions, distinguishing direct causation from reverse causality (e.g., "chemical coping") remains difficult. This study uses Mendelian Randomization (MR) to estimate the causal effect of alcohol consumption on depression, anxiety, PTSD, and alcohol use disorders. MATERIALS AND METHODS: We conducted a retrospective MR study using data from the National Institutes of Health (NIH) All of Us Research Program (Controlled Tier Dataset v7). We utilized two genetic variants strongly associated with alcohol consumption, rs671 (in the ALDH2 gene) and rs1229984 (in the ADH1B gene), as instrumental variables. Mental health and alcohol-related outcomes were defined by Electronic Health Record (EHR) diagnoses. Self-reported alcohol consumption was derived from the AUDIT-C survey. Logistic regression was performed within genetic ancestry groups, followed by a random-effects meta-analysis. RESULTS: Observational data demonstrated large, highly significant observational correlations. For example, heavy drinkers (10+ drinks, 4+ times/week) were 3.29 times more likely to have PTSD than light drinkers (1-2 drinks, monthly or less), and adjusted models showed an odds ratio (OR) of 8.88 for PTSD if diagnosed with an alcohol condition. Despite these strong observational correlations, MR meta-analyses utilizing rs1229984 and rs671 yielded null causal estimates for PTSD, depression, and anxiety (MR ORs near 1.0), while confirming genetically predicted alcohol consumption is definitively causal for alcohol-related conditions. CONCLUSIONS: This MR study demonstrates that alcohol consumption is not a major instigating cause of PTSD, depression, or anxiety. The strong epidemiological correlation between alcohol use disorders and psychiatric comorbidities is likely driven by "chemical coping" (self-medication) or shared confounding factors, rather than direct alcohol exposure. Additional MR studies are required to confirm the "chemical coping" (self-medication) hypothesis of these mental health conditions driving alcohol use.