Causal associations between type 1 diabetes and COVID-19 infection and prognosis: a two-sample Mendelian randomization study

Introduction It has been suggested that type 1 diabetes was associated with increased COVID-19 morbidity and mortality. However, their causal relationship is still unclear. Herein, we performed a two-sample Mendelian randomization (MR) to investigate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. Research design and methods The summary statistics of type 1 diabetes were obtained from two published genome-wide association studies of European population, one as a discovery sample including 15 573 cases and 158 408 controls, and the other data as a replication sample consisting of 5913 cases and 8828 controls. We first performed a two-sample MR analysis to evaluate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. Then, reverse MR analysis was conducted to determine whether reverse causality exists. Results MR analysis results showed that the genetically predicted type 1 diabetes was associated with higher risk of severe COVID-19 (OR=1.073, 95% CI: 1.034 to 1.114, p FDR =1.15×10 −3 ) and COVID-19 death (OR=1.075, 95% CI: 1.033 to 1.119, p FDR =1.15×10 −3 ). Analysis of replication dataset showed similar results, namely a positive association between type 1 diabetes and severe COVID-19 (OR=1.055, 95% CI: 1.029 to 1.081, p FDR =1.59×10 −4 ), and a positively correlated association with COVID-19 death (OR=1.053, 95% CI: 1.026 to 1.081, p FDR =3.50×10 −4 ). No causal association was observed between type 1 diabetes and COVID-19 positive, hospitalized COVID-19, the time to the end of COVID-19 symptoms in the colchicine treatment group and placebo treatment group. Reverse MR analysis showed no reverse causality. Conclusions Type 1 diabetes had a causal effect on severe COVID-19 and death after COVID-19 infection. Further mechanistic studies are needed to explore the relationship between type 1 diabetes and COVID-19 infection and prognosis.