Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals
Kosmicki JA., Horowitz JE., Banerjee N., Lanche R., Marcketta A., Maxwell E., Bai X., Sun D., Backman JD., Sharma D., Kury FSP., Kang HM., O'Dushlaine C., Yadav A., Mansfield AJ., Li AH., Watanabe K., Gurski L., McCarthy SE., Locke AE., Khalid S., O'Keeffe S., Mbatchou J., Chazara O., Huang Y., Kvikstad E., O'Neill A., Nioi P., Parker MM., Petrovski S., Runz H., Szustakowski JD., Wang Q., Wong E., Cordova-Palomera A., Smith EN., Szalma S., Zheng X., Esmaeeli S., Davis JW., Lai YP., Chen X., Justice AE., Leader JB., Mirshahi T., Carey DJ., Verma A., Sirugo G., Ritchie MD., Rader DJ., Povysil G., Goldstein DB., Kiryluk K., Pairo-Castineira E., Rawlik K., Pasko D., Walker S., Meynert A., Kousathanas A., Moutsianas L., Tenesa A., Caulfield M., Scott R., Wilson JF., Baillie JK., Butler-Laporte G., Nakanishi T., Lathrop M., Richards JB., Jones M., Balasubramanian S., Salerno W., Shuldiner AR., Marchini J., Overton JD., Habegger L., Cantor MN., Reid JG., Baras A., Abecasis GR., Ferreira MAR.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.