Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis

BMC Medical Genomics

Research

Jaspal S. Kooner¹  Raabia Farooqi²  Weihua Zhang³ 

[1]Department of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust, UB1 3HW, Middlesex, UK

[2]National Heart and Lung Institute, Imperial College London, W12 0NN, London, UK

[3]Imperial College Healthcare NHS Trust, W12 0HS, London, UK

[4]MRC-PHE Centre for Environment and Health, Imperial College London, W2 1PG, London, UK

[5]Department of Epidemiology and Biostatistics, Imperial College London, W2 1PG, London, UK

[6]Department of Epidemiology and Biostatistics, Imperial College London, W2 1PG, London, UK

[7]Department of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust, UB1 3HW, Middlesex, UK

关键词: COVID-19;    Polygenic Risk Score;    Black Asian Minority Ethnic;    susceptibility;    severity;    genetic risk;   

DOI  :  10.1186/s12920-023-01584-x

 received in 2022-11-30, accepted in 2023-06-16,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

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