Host Genetic Liability for Severe COVID-19 Associates with Alcohol Drinking Behavior and Diabetic Outcomes in Participants of European Descent

Risk factors and long-term consequences of COVID-19 infection are unclear but can be investigated with large-scale genomic data. To distinguish correlation from causation, we performed in-silico analyses of three COVID-19 outcomes (N > 1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use (genetic causality proportion (gĉp) with severe respiratory COVID-19 = 0.576, p = 1.07 × 10−5 and hospitalized COVID-19 = 0.713, p = 0.003), and alcohol drinking status (gĉp with severe respiratory COVID-19 = 0.633, p = 7.04 × 10−5 and hospitalized COVID-19 = 0.848, p = 4.13 × 10−13). COVID-19 risk loci associated with several hematologic biomarkers. Comprehensive findings inform genetic contributions to COVID-19 epidemiology, molecular mechanisms, and risk factors and potential long-term health effects of severe response to infection.