Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population
COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The severity of COVID-19 is highly variable and related to known (e.g., age, obesity, immune deficiency) and unknown risk factors. The widespread clinical symptoms encompass a large group of asymptomatic COVID-19 pat...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844918/ https://www.ncbi.nlm.nih.gov/pubmed/36649279 http://dx.doi.org/10.1371/journal.pone.0276700 |
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author | Shen, Yiran Khatri, Bhuwan Rananaware, Santosh Li, Danmeng Ostrov, David A. Jain, Piyush K. Lessard, Christopher J. Nguyen, Cuong Q. |
author_facet | Shen, Yiran Khatri, Bhuwan Rananaware, Santosh Li, Danmeng Ostrov, David A. Jain, Piyush K. Lessard, Christopher J. Nguyen, Cuong Q. |
author_sort | Shen, Yiran |
collection | PubMed |
description | COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The severity of COVID-19 is highly variable and related to known (e.g., age, obesity, immune deficiency) and unknown risk factors. The widespread clinical symptoms encompass a large group of asymptomatic COVID-19 patients, raising a crucial question regarding genetic susceptibility, e.g., whether individual differences in immunity play a role in patient symptomatology and how much human leukocyte antigen (HLA) contributes to this. To reveal genetic determinants of susceptibility to COVID-19 severity in the population and further explore potential immune-related factors, we performed a genome-wide association study on 284 confirmed COVID-19 patients (cases) and 95 healthy individuals (controls). We compared cases and controls of European (EUR) ancestry and African American (AFR) ancestry separately. We identified two loci on chromosomes 5q32 and 11p12, which reach the significance threshold of suggestive association (p<1x10(-5) threshold adjusted for multiple trait testing) and are associated with the COVID-19 susceptibility in the European ancestry (index rs17448496: odds ratio[OR] = 0.173; 95% confidence interval[CI], 0.08–0.36 for G allele; p = 5.15× 10(−5) and index rs768632395: OR = 0.166; 95% CI, 0.07–0.35 for A allele; p = 4.25×10(−6), respectively), which were associated with two genes, PPP2R2B at 5q32, and LRRC4C at 11p12, respectively. To explore the linkage between HLA and COVID-19 severity, we applied fine-mapping analysis to dissect the HLA association with mild and severe cases. Using In-silico binding predictions to map the binding of risk/protective HLA to the viral structural proteins, we found the differential presentation of viral peptides in both ancestries. Lastly, extrapolation of the identified HLA from the cohort to the worldwide population revealed notable correlations. The study uncovers possible differences in susceptibility to COVID-19 in different ancestral origins in the genetic background, which may provide new insights into the pathogenesis and clinical treatment of the disease. |
format | Online Article Text |
id | pubmed-9844918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98449182023-01-18 Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population Shen, Yiran Khatri, Bhuwan Rananaware, Santosh Li, Danmeng Ostrov, David A. Jain, Piyush K. Lessard, Christopher J. Nguyen, Cuong Q. PLoS One Research Article COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The severity of COVID-19 is highly variable and related to known (e.g., age, obesity, immune deficiency) and unknown risk factors. The widespread clinical symptoms encompass a large group of asymptomatic COVID-19 patients, raising a crucial question regarding genetic susceptibility, e.g., whether individual differences in immunity play a role in patient symptomatology and how much human leukocyte antigen (HLA) contributes to this. To reveal genetic determinants of susceptibility to COVID-19 severity in the population and further explore potential immune-related factors, we performed a genome-wide association study on 284 confirmed COVID-19 patients (cases) and 95 healthy individuals (controls). We compared cases and controls of European (EUR) ancestry and African American (AFR) ancestry separately. We identified two loci on chromosomes 5q32 and 11p12, which reach the significance threshold of suggestive association (p<1x10(-5) threshold adjusted for multiple trait testing) and are associated with the COVID-19 susceptibility in the European ancestry (index rs17448496: odds ratio[OR] = 0.173; 95% confidence interval[CI], 0.08–0.36 for G allele; p = 5.15× 10(−5) and index rs768632395: OR = 0.166; 95% CI, 0.07–0.35 for A allele; p = 4.25×10(−6), respectively), which were associated with two genes, PPP2R2B at 5q32, and LRRC4C at 11p12, respectively. To explore the linkage between HLA and COVID-19 severity, we applied fine-mapping analysis to dissect the HLA association with mild and severe cases. Using In-silico binding predictions to map the binding of risk/protective HLA to the viral structural proteins, we found the differential presentation of viral peptides in both ancestries. Lastly, extrapolation of the identified HLA from the cohort to the worldwide population revealed notable correlations. The study uncovers possible differences in susceptibility to COVID-19 in different ancestral origins in the genetic background, which may provide new insights into the pathogenesis and clinical treatment of the disease. Public Library of Science 2023-01-17 /pmc/articles/PMC9844918/ /pubmed/36649279 http://dx.doi.org/10.1371/journal.pone.0276700 Text en © 2023 Shen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shen, Yiran Khatri, Bhuwan Rananaware, Santosh Li, Danmeng Ostrov, David A. Jain, Piyush K. Lessard, Christopher J. Nguyen, Cuong Q. Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population |
title | Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population |
title_full | Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population |
title_fullStr | Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population |
title_full_unstemmed | Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population |
title_short | Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population |
title_sort | ancestral origins are associated with sars-cov-2 susceptibility and protection in a florida patient population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844918/ https://www.ncbi.nlm.nih.gov/pubmed/36649279 http://dx.doi.org/10.1371/journal.pone.0276700 |
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