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

Frank R Wendt; Antonella De Lillo; Gita A Pathak; Flavio De Angelis; COVID-19 Host Genetics Initiative; Renato Polimanti

doi:10.3389/fgene.2021.765247

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

Front Genet. 2021 Dec 13:12:765247. doi: 10.3389/fgene.2021.765247. eCollection 2021.

Authors

Frank R Wendt^{1

2}, Antonella De Lillo¹, Gita A Pathak^{1

2}, Flavio De Angelis^{1

2}; COVID-19 Host Genetics Initiative; Renato Polimanti^{1

2}

Affiliations

¹ Division of Human Genetics in Psychiatry, Yale School of Medicine, New Haven, CT, United States.
² VA CT Healthcare System, West Haven, CT, United States.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; alcohol; causal inference; diabetes; genetic overlap.

Abstract

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