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A catalog of associations between rare coding variants and COVID-19 outcomes #MMPMID33655273
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 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 MA
medRxiv 2021[Feb]; ä (ä): ä PMID33655273show ga
Severe 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.