TY - JOUR
T1 - Exome-Wide Association Study Reveals Host Genetic Variants Likely Associated with the Severity of COVID-19 in Patients of European Ancestry
AU - Upadhyai, Priyanka
AU - Shenoy, Pooja U.
AU - Banjan, Bhavya
AU - Albeshr, Mohammed F.
AU - Mahboob, Shahid
AU - Manzoor, Irfan
AU - Das, Ranajit
N1 - Funding Information:
We thank the GEN-COVID consortium, University of Siena, Italy for kind donation of the COVID-19 exome data. The authors also thank the Researchers Supporting Project, King Saud University, Riyadh, Saudi Arabia for the APC support.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - Host genetic variability plays a pivotal role in modulating COVID-19 clinical outcomes. Despite the functional relevance of protein-coding regions, rare variants located here are less likely to completely explain the considerable numbers of acutely affected COVID-19 patients worldwide. Using an exome-wide association approach, with individuals of European descent, we sought to identify common coding variants linked with variation in COVID-19 severity. Herein, cohort 1 compared non-hospitalized (controls) and hospitalized (cases) individuals, and in cohort 2, hospitalized subjects requiring respiratory support (cases) were compared to those not requiring it (controls). 229 and 111 variants differed significantly between cases and controls in cohorts 1 and 2, respectively. This included FBXO34, CNTN2, and TMCC2 previously linked with COVID-19 severity using association studies. Overall, we report SNPs in 26 known and 12 novel candidate genes with strong molecular evidence implicating them in the pathophysiology of life-threatening COVID-19 and post-recovery sequelae. Of these few notable known genes include, HLA-DQB1, AHSG, ALOX5AP, MUC5AC, SMPD1, SPG7, SPEG, GAS6, and SERPINA12. These results enhance our understanding of the pathomechanisms underlying the COVID-19 clinical spectrum and may be exploited to prioritize biomarkers for predicting disease severity, as well as to improve treatment strategies in individuals of European ancestry.
AB - Host genetic variability plays a pivotal role in modulating COVID-19 clinical outcomes. Despite the functional relevance of protein-coding regions, rare variants located here are less likely to completely explain the considerable numbers of acutely affected COVID-19 patients worldwide. Using an exome-wide association approach, with individuals of European descent, we sought to identify common coding variants linked with variation in COVID-19 severity. Herein, cohort 1 compared non-hospitalized (controls) and hospitalized (cases) individuals, and in cohort 2, hospitalized subjects requiring respiratory support (cases) were compared to those not requiring it (controls). 229 and 111 variants differed significantly between cases and controls in cohorts 1 and 2, respectively. This included FBXO34, CNTN2, and TMCC2 previously linked with COVID-19 severity using association studies. Overall, we report SNPs in 26 known and 12 novel candidate genes with strong molecular evidence implicating them in the pathophysiology of life-threatening COVID-19 and post-recovery sequelae. Of these few notable known genes include, HLA-DQB1, AHSG, ALOX5AP, MUC5AC, SMPD1, SPG7, SPEG, GAS6, and SERPINA12. These results enhance our understanding of the pathomechanisms underlying the COVID-19 clinical spectrum and may be exploited to prioritize biomarkers for predicting disease severity, as well as to improve treatment strategies in individuals of European ancestry.
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U2 - 10.3390/life12091300
DO - 10.3390/life12091300
M3 - Article
AN - SCOPUS:85138677467
SN - 0024-3019
VL - 12
JO - Life
JF - Life
IS - 9
M1 - 1300
ER -