Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program.

Peloso GM, Tcheandjieu C, McGeary JE, Posner DC, Ho YL, Zhou JJ, Hilliard AT, Joseph J, O'Donnell CJ, Efird JT, Crawford DC, Wu WC, Arjomandi M, VA Million Veteran Program COVID-19 Science Initiative, Sun YV, Assimes TL, Huffman JE. Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program. Frontiers in genetics. 2022 Feb 3; 12:777076.

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Abstract:

SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association study (GWAS) for COVID-19 outcomes identified four independent genetic variants (rs8176719, rs73062389, rs60870724, and rs73910904) contributing to COVID-19 positivity, including one novel locus found exclusively among Hispanics. We replicated eight of nine previously reported genetic associations at an alpha of 0.05 in at least one population-specific or the multi-population meta-analysis for one of the four MVP COVID-19 outcomes. We used rs8176719 and three additional variants to accurately infer ABO blood types. We found that A, AB, and B blood types were associated with testing positive for COVID-19 compared with O blood type with the highest risk for the A blood group. We did not observe any genome-wide significant associations for COVID-19 severity outcomes among those testing positive. Our study replicates prior GWAS findings associated with testing positive for COVID-19 among mostly White samples and extends findings at three loci to Black and Hispanic individuals. We also report a new locus among Hispanics requiring further investigation. These findings may aid in the identification of novel therapeutic agents to decrease the morbidity and mortality of COVID-19 across all major ancestral populations.