Genetic risk of type 2 diabetes and its relationship to severe Covid-19 disease

Abstract

Type 2 diabetes (T2D) is a risk factor for severe cases of Covid-19. T2D is partially heritable, though few studies have examined the role of T2D genetic risk factors in severe Covid-19. We analyzed data from 459,493 participants in the UK Biobank for association of a T2D polygenic risk score (PRS) with severe Covid-19 outcomes diagnosed between February 1, 2020 and October 31, 2022. Participants with severe Covid-19 (SC, N=8,367) were those hospitalized for Covid-19 (ICD-10 codes U07.1 or U07.2) or who died of Covid-19. Logistic regression using SC (yes/no) as the outcome was employed, adjusting for age, sex and the first ten principal components to account for potential population stratification. We found positive and statistically significant relationships between the T2D PRS and SC. Among all participants, each SD unit increase in PRS was associated with an odds ratio of 1.09 (95% CI= 1.06 – 1.11; p=1.7e-12) for risk of SC. Examined as a categorical variable, participants within the top T2D PRS quintile had 18% (95% CI= 11% – 27%; p=9.1e-7) higher risks of SC in comparison to participants in the median (40%-60%) T2D PRS quintile. To address potential issues with selection bias, we repeated our analyses using three alternative control groups including those who (i) had never been diagnosed with Covid-19 at time of data collection, (ii) had non-severe Covid-19, or (iii) had undergone Covid-19-testing (regardless of their test results), obtaining very similar results. The T2D PRS was also predictive of severe Covid-19 among participants with no diagnosis of T2D. These results imply that genetic factors associated with T2D influence susceptibility to SC outcomes, providing support for the potential use of PRS in assessing patient risks and furthering our understanding of the mechanisms underlying the increased risk of SC among individuals with T2D.