Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis
Abstract Background COVID-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...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-023-01584-x |
| _version_ | 1797789518637563904 |
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| author | Raabia Farooqi Jaspal S. Kooner Weihua Zhang |
| author_facet | Raabia Farooqi Jaspal S. Kooner Weihua Zhang |
| author_sort | Raabia Farooqi |
| collection | DOAJ |
| description | Abstract Background COVID-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. Methods We 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). Results Compared 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. Conclusions Significant 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. |
| first_indexed | 2024-03-13T01:51:52Z |
| format | Article |
| id | doaj.art-b4bda1dcd21f4697934f02170a280f6e |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-13T01:51:52Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-b4bda1dcd21f4697934f02170a280f6e2023-07-02T11:29:11ZengBMCBMC Medical Genomics1755-87942023-06-0116111510.1186/s12920-023-01584-xAssociations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysisRaabia Farooqi0Jaspal S. Kooner1Weihua Zhang2Department of Epidemiology and Biostatistics, Imperial College LondonDepartment of Cardiology, Ealing Hospital, London North West University Healthcare NHS TrustDepartment of Epidemiology and Biostatistics, Imperial College LondonAbstract Background COVID-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. Methods We 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). Results Compared 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. Conclusions Significant 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.https://doi.org/10.1186/s12920-023-01584-xCOVID-19Polygenic Risk ScoreBlack Asian Minority Ethnicsusceptibilityseveritygenetic risk |
| spellingShingle | Raabia Farooqi Jaspal S. Kooner Weihua Zhang Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis BMC Medical Genomics COVID-19 Polygenic Risk Score Black Asian Minority Ethnic susceptibility severity genetic risk |
| title | Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis |
| title_full | Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis |
| title_fullStr | Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis |
| title_full_unstemmed | Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis |
| title_short | Associations between polygenic risk score and covid-19 susceptibility and severity across ethnic groups: UK Biobank analysis |
| title_sort | associations between polygenic risk score and covid 19 susceptibility and severity across ethnic groups uk biobank analysis |
| topic | COVID-19 Polygenic Risk Score Black Asian Minority Ethnic susceptibility severity genetic risk |
| url | https://doi.org/10.1186/s12920-023-01584-x |
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