A catalog of associations between rare coding variants and COVID-19 outcomes
Kosmicki JA., Horowitz JE., Banerjee N., Lanche R., Marcketta A., Maxwell E., Bai X., Sun D., Backman JD., Sharma D., 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 Y-P., 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 MA.
ABSTRACTSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 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 (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 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, with results publicly browsable at https://rgc-covid19.regeneron.com.