A catalog of associations between rare coding variants and COVID-19 outcomes

• DOI: 10.1101/2020.10.28.20221804
• Publication Date: 2020-11-03T22:15:39Z
• Authors: J. A. Kosmicki; J. E. Horowitz; N. Banerjee; R. Lanche; A. Marcketta; E. Maxwell; X. Bai; D. Sun; J. D. Backman; D. Sharma; H. M. Kang; C. O’Dushlaine; A. Yadav; A. J. Mansfield; A. H. Li; K. Watanabe; L. Gurski; S. E. McCarthy; A. E. Locke; S. Khalid; S. O’Keeffe; J. Mbatchou; O. Chazara; Y. Huang; E. Kvikstad; A. O’Neill; P. Nioi; M. M. Parker; S. Petrovski; H. Runz; J. D. Szustakowski; Q. Wang; E. Wong; A. Cordova-Palomera; E. N. Smith; S. Szalma; X. Zheng; S. Esmaeeli; J. W. Davis; Y-P. Lai; X. Chen; A. E. Justice; J. B. Leader; T. Mirshahi; D. J. Carey; A. Verma; G. Sirugo; M. D. Ritchie; D. J. Rader; G. Povysil; D. B. Goldstein; K. Kiryluk; E. Pairo-Castineira; K. Rawlik; D. Pasko; S. Walker; A. Meynert; A. Kousathanas; L. Moutsianas; A. Tenesa; M. Caulfield; R. Scott; J. F. Wilson; J. K. Baillie; G. Butler-Laporte; T. Nakanishi; M. Lathrop; J.B. Richards; ; ; M. Jones; S. Balasubramanian; W. Salerno; A. R. Shuldiner; J. Marchini; J. D. Overton; L. Habegger; M. N. Cantor; J. G. Reid; A. Baras; G. R. Abecasis; M. A. Ferreira
• Keywords: Genome-wide Association Study; Exome; Coronavirus

ABSTRACT Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear either exome-wide when specifically focusing on (i) 14 interferon pathway genes which deleterious have been reported severe patients; (ii) 167 located GWAS risk loci; (iii) 32 additional of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant protein-coding detectable effect sizes at our current sample sizes. Analyses will be updated as data become available, results publicly browsable https://rgc-covid19.regeneron.com .