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

ABSTRACT: Type 2 diabetes (T2D) is known as one of the important risk factors for the severity and mortality of COVID-19. Here, we evaluate the impact of T2D and its genetic susceptibility on the severity and mortality of COVID-19, using 459,119 individuals in UK Biobank. Utilizing the polygenic risk scores (PRS) for T2D, we identified a significant association between T2D or T2D PRS, and COVID-19 severity. We further discovered the efficacy of vaccination and the pivotal role of T2D-related genetics in the pathogenesis of severe COVID-19. Moreover, we found that individuals with T2D or those in the high T2D PRS group had a significantly increased mortality rate. We also observed that the mortality rate for SARS-CoV-2-infected patients was approximately 2 to 7 times higher than for those not infected, depending on the time of infection. These findings emphasize the potential of T2D PRS in estimating the severity and mortality of COVID-19.

SUBMITTER: Lee A

PROVIDER: S-EPMC10808197 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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

Lee Aeyeon A Seo Jieun J Park Seunghwan S Cho Youngkwang Y Kim Gaeun G Li Jun J Liang Liming L Park Taesung T Chung Wonil W

Communications biology 20240124 1

Type 2 diabetes (T2D) is known as one of the important risk factors for the severity and mortality of COVID-19. Here, we evaluate the impact of T2D and its genetic susceptibility on the severity and mortality of COVID-19, using 459,119 individuals in UK Biobank. Utilizing the polygenic risk scores (PRS) for T2D, we identified a significant association between T2D or T2D PRS, and COVID-19 severity. We further discovered the efficacy of vaccination and the pivotal role of T2D-related genetics in t ...[more]

PMID: 38267566

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Project description:BackgroundThis study explored whether the prospective associations between muscle strength and incident type 2 diabetes (T2D) differ by varying levels of genetic susceptibility to T2D.MethodsThis study included 141,848 white British individuals from the UK Biobank. Muscle strength was expressed as the relative value of grip strength (measured by a hand dynamometer) divided by fat-free mass (measured via bioelectrical impedance analysis). Three categories of muscle strength (low, medium and high) were generated based on the sex- and age-specific tertiles. Genetic risk of T2D was estimated using a weighted polygenic risk score based on 138 independent single-nucleotide polymorphisms for T2D. During a median 7.4-year follow-up, 4,743 incident T2D cases were accrued. Cox regression with age as the underlying timescale was fit.ResultsHigh muscle strength was associated with a 44% lower hazard of T2D (HR:0.56, 95%CI:0.52-0.60), compared with low muscle strength, after adjustment for genetic risk of T2D. The inverse association between muscle strength and incident T2D was weaker in individuals with high genetic susceptibility. There was evidence of interaction between muscle strength and genetic susceptibility to T2D (p-additive = 0.010, p-multiplicative = 0.046). The estimated 8-year absolute risk of T2D was lower for high genetic risk-high muscle strength (2.47%), compared with low (2.89%) or medium (4.00%) genetic risk combined with low muscle strength.ConclusionsHigher muscle strength was associated with lower relative risk of developing T2D, irrespective of genetic susceptibility to T2D, while such association was weaker in the high genetic risk group. Individuals at high genetic risk of T2D but with high muscle strength may have a lower 8-year absolute risk of developing T2D, compared with those at low or medium genetic risk but with low muscle strength. Our findings inform future clinical trials to prevent or delay the onset of T2D by implementing muscle-strengthening interventions among individuals of varying levels of genetic susceptibility to T2D, including those with high genetic risk.

Project description:BackgroundCOVID-19 manifests with huge heterogeneity in susceptibility and severity outcomes. UK Black Asian and Minority Ethnic (BAME) groups have demonstrated disproportionate burdens. Some variability remains unexplained, suggesting potential genetic contribution. Polygenic Risk Scores (PRS) can determine genetic predisposition to disease based on Single Nucleotide Polymorphisms (SNPs) within the genome. COVID-19 PRS analyses within non-European samples are extremely limited. We applied a multi-ethnic PRS to a UK-based cohort to understand genetic contribution to COVID-19 variability.MethodsWe constructed two PRS for susceptibility and severity outcomes based on leading risk-variants from the COVID-19 Host Genetics Initiative. Scores were applied to 447,382 participants from the UK-Biobank. Associations with COVID-19 outcomes were assessed using binary logistic regression and discriminative power was validated using incremental area under receiver operating curve (ΔAUC). Variance explained was compared between ethnic groups via incremental pseudo-R2 (ΔR2).ResultsCompared to those at low genetic risk, those at high risk had a significantly greater risk of severe COVID-19 for White (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42-1.74), Asian (OR 2.88, 95% CI 1.63-5.09) and Black (OR 1.98, 95% CI 1.11-3.53) ethnic groups. Severity PRS performed best within Asian (ΔAUC 0.9%, ΔR2 0.98%) and Black (ΔAUC 0.6%, ΔR2 0.61%) cohorts. For susceptibility, higher genetic risk was significantly associated with COVID-19 infection risk for the White cohort (OR 1.31, 95% CI 1.26-1.36), but not for Black or Asian groups.ConclusionsSignificant associations between PRS and COVID-19 outcomes were elicited, establishing a genetic basis for variability in COVID-19. PRS showed utility in identifying high-risk individuals. The multi-ethnic approach allowed applicability of PRS to diverse populations, with the severity model performing well within Black and Asian cohorts. Further studies with larger sample sizes of non-White samples are required to increase statistical power and better assess impacts within BAME populations.

Dataset Information

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

Publications

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

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