Shared genetic architecture between type 2 diabetes and COVID-19 severity

Abstract

Purpose Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. Methods By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. Results Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization ( r g = 0.156, SE = 0.057, p = 0.005) or severe disease ( r g = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having p gene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. Conclusions Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets. Supplementary Information The online version contains supplementary material available at 10.1007/s40618-022-01920-5.

Eliminating COVID‐19 as the immediate culprit for igniting pancreatitis

“…Furthermore, the analysis reveals an elevated risk of developing T2D in individuals with severe and hospitalized cases of COVID‐19. Nevertheless, some MR investigations have shown that there may not be a substantial correlation between T2D and the phenotype of COVID‐19 37,38 . In their review, Grubišić et al 39 proposed that COVID‐19 can potentially trigger the development of diabetes via the induction of immunological imbalance and glucose metabolism disruption.…”

“…and the phenotype of COVID-19. 37,38 In their review, Grubišić et al 39 proposed that COVID-19 can potentially trigger the development of diabetes via the induction of immunological imbalance and glucose metabolism disruption. There exists a strong correlation between hyperglycemia and several factors, such as the duration of hospitalization, 40 the incidence of infection, 41 and the deterioration of patient outcomes 42 in individuals diagnosed with AP.…”

Identification of common genes and pathways between type 2 diabetes and COVID-19

“…COVID-19 is highly infectious, shows rapid mutation, and has become a global pandemic, resulting in high morbidity and mortality due to complications . Previous studies have shown a significant genetic correlation between T2DM and COVID-19 (Wu K. C. H. et al, 2022;Ni et al, 2023). Furthermore, Mendelian randomization has demonstrated a causal relationship between genetic susceptibility to T2DM and SARS-CoV-2 infection and hospitalization due to COVID-19 (Host Genetics Initiative, 2022).…”

Type 2 diabetes and its genetic susceptibility are associated with increased severity and mortality of COVID-19 in UK Biobank

“…This is supported by extensive population-based genome-wide association studies (GWAS), which suggest that a number of common genetic variants can affect the severity of symptoms following a COVID-19 infection 4 , 19 . The genes most strongly associated with severe COVID-19 progression, as identified by GWAS, typically play roles in immune response mechanisms, lung disease pathology, CVD 20 , and T2D 21 .…”