48 Assessing Causal Associations of T2D and Obesity with Severe COVID-19 Using Mendelian Randomization

Oregon Convention Center 

Observational studies have reported high comorbidity between type 2 diabetes (T2D), obesity, and severe COVID-19. However, the causality among T2D, obesity, and severe COVID-19 has not yet been fully validated. We performed genetic correlation and Mendelian randomization (MR) analyses to assess genetic relationships and potential causal associations of T2D and obesity with two COVID-19 outcomes: SARS-CoV-2 infection and COVID-19 severity. Our study incorporated two-sample MR, one-sample MR, and nonlinear MR analyses, utilizing summary-level and individual-level data from the GIANT and DIAGRAM consortia, and the UK Biobank. We identified a high genetic overlap between T2D and each of the COVID-19 outcomes. The two-sample MR analyses indicate that genetic liability to T2D confers a causal effect on COVID-19 severity (beta=0.1500, p=0.0012), and genetic liability to body mass index (BMI) exerts a causal effect on COVID-19 severity (beta=0.3958, p=4.36e-18). The results from the one-sample and nonlinear MR analyses suggest similar causal relationships of T2D and BMI with COVID-19 outcomes. Our analyses conclude that T2D and obesity are causal risk factors for COVID-19 severity.

Mendelian Randomization

Causal Inference

Type 2 diabetes

Obesity

COVID-19 

Section on Statistics in Genomics and Genetics