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. 2023 Jun;11(3):e003167.
doi: 10.1136/bmjdrc-2022-003167.

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

Xin-Ling Ma #  1   2 , Qi-Yun Shi #  3 , Qi-Gang Zhao  1   2 , Qian Xu  1   2 , Shan-Shan Yan  1   2 , Bai-Xue Han  1   2 , Chen Fang  3 , Lei Zhang  4   5 , Yu-Fang Pei  6   2
Affiliations

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

Xin-Ling Ma et al. BMJ Open Diabetes Res Care. 2023 Jun.

Abstract

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, pFDR=1.15×10-3) and COVID-19 death (OR=1.075, 95% CI: 1.033 to 1.119, pFDR=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, pFDR=1.59×10-4), and a positively correlated association with COVID-19 death (OR=1.053, 95% CI: 1.026 to 1.081, pFDR=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.

Keywords: COVID-19; Diabetes Mellitus, Type 1; Infections; Prognosis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Outline of the MR analysis. GWAS, genome-wide association study; LD, linkage disequilibrium; MR, Mendelian randomization; SNPs, single-nucleotide polymorphisms.
Figure 2
Figure 2
Result of leave-one-out test of type 1 diabetes on severe COVID-19. The bottom black line represents the estimated value of the IVW analysis. IVW, inverse variance weighted; MR, Mendelian randomization.
Figure 3
Figure 3
Result of leave-one-out test of type 1 diabetes on COVID-19 death. The bottom black line represents the estimated value of the IVW analysis. IVW, inverse variance weighted; MR, Mendelian randomization.
See this image and copyright information in PMC

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