PMID- 36649279 OWN - NLM STAT- MEDLINE DCOM- 20230120 LR - 20230313 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 18 IP - 1 DP - 2023 TI - Ancestral origins are associated with SARS-CoV-2 susceptibility and protection in a Florida patient population. PG - e0276700 LID - 10.1371/journal.pone.0276700 [doi] LID - e0276700 AB - 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 = 5.15x 10-5 and index rs768632395: OR = 0.166; 95% CI, 0.07-0.35 for A allele; p = 4.25x10-6, 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. CI - Copyright: (c) 2023 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Shen, Yiran AU - Shen Y AUID- ORCID: 0000-0002-4220-6862 AD - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America. FAU - Khatri, Bhuwan AU - Khatri B AUID- ORCID: 0000-0001-5456-2963 AD - Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America. FAU - Rananaware, Santosh AU - Rananaware S AUID- ORCID: 0000-0001-8789-5799 AD - Department of Chemical Engineering, University of Florida, Gainesville, Florida, United States of America. FAU - Li, Danmeng AU - Li D AUID- ORCID: 0000-0002-6905-554X AD - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America. FAU - Ostrov, David A AU - Ostrov DA AD - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America. FAU - Jain, Piyush K AU - Jain PK AUID- ORCID: 0000-0001-7153-442X AD - Department of Chemical Engineering, University of Florida, Gainesville, Florida, United States of America. FAU - Lessard, Christopher J AU - Lessard CJ AUID- ORCID: 0000-0003-2440-3843 AD - Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America. FAU - Nguyen, Cuong Q AU - Nguyen CQ AUID- ORCID: 0000-0001-5633-4075 AD - Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America. AD - Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America. AD - Center of Orphaned Autoimmune Diseases, University of Florida, Gainesville, Florida, United States of America. LA - eng GR - R01 DE028544/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230117 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) SB - IM MH - Humans MH - *COVID-19/epidemiology/genetics MH - Florida MH - *Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - Histocompatibility Antigens Class I/genetics MH - HLA Antigens MH - SARS-CoV-2 MH - White/genetics MH - Black or African American/genetics PMC - PMC9844918 COIS- The authors have declared that no competing interests exist. EDAT- 2023/01/18 06:00 MHDA- 2023/01/20 06:00 PMCR- 2023/01/17 CRDT- 2023/01/17 13:43 PHST- 2022/04/12 00:00 [received] PHST- 2022/10/11 00:00 [accepted] PHST- 2023/01/17 13:43 [entrez] PHST- 2023/01/18 06:00 [pubmed] PHST- 2023/01/20 06:00 [medline] PHST- 2023/01/17 00:00 [pmc-release] AID - PONE-D-22-10827 [pii] AID - 10.1371/journal.pone.0276700 [doi] PST - epublish SO - PLoS One. 2023 Jan 17;18(1):e0276700. doi: 10.1371/journal.pone.0276700. eCollection 2023.