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

Xin-Ling Ma; Qi-Yun Shi; Qi-Gang Zhao; Qian Xu; Shan-Shan Yan; Bai-Xue Han; Chen Fang; Lei Zhang; Yu-Fang Pei

doi:10.1136/bmjdrc-2022-003167

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

BMJ Open Diabetes Res Care. 2023 Jun;11(3):e003167. doi: 10.1136/bmjdrc-2022-003167.

Authors

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 Fang³, Lei Zhang^{4

5}, Yu-Fang Pei^{6

2}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
² Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
³ Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁴ Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China ypei@suda.edu.cn lzhang6@suda.edu.cn.
⁵ Center for Genetic Epidemiology and Genomics, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
⁶ Department of Epidemiology and Biostatistics, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China ypei@suda.edu.cn lzhang6@suda.edu.cn.

^# Contributed equally.

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, 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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / epidemiology
COVID-19* / genetics
Diabetes Mellitus, Type 1* / epidemiology
Diabetes Mellitus, Type 1* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis