A Multitrait Locus Regulates Sarbecovirus Pathogenesis

• DOI: 10.1101/2022.06.01.494461
• Publication Date: 2022-06-03T01:25:16Z
• Authors: Alexandra Schäfer; Sarah R. Leist; Lisa E. Gralinski; David R. Martinez; Emma S. Winkler; Kenichi Okuda; Padraig E. Hawkins; Kendra L Gully; Rachel L. Graham; D. Trevor Scobey; Timothy A. Bell; Pablo Hock; Ginger D. Shaw; Jennifer F. Loome; Emily A. Madden; Elizabeth Anderson; Victoria K. Baxter; Sharon A. Taft-Benz; Mark R. Zweigart; Samantha R. May; Stephanie Dong; Matthew Clark; Darla R. Miller; Rachel M Lynch; Mark T. Heise; Roland Tisch; Richard C. Boucher; Fernando Pardo Ma...; Stephanie A. Mont...; Michael S. Diamond; Martin T. Ferris; Ralph S. Baric
• Keywords: Synteny; Genome-wide Association Study; Genetic Association; Human genetics

Infectious diseases have shaped the human population genetic structure, and variation influences susceptibility to many viral diseases. However, a variety of challenges made implementation traditional Genome-wide Association Studies (GWAS) approaches study these infectious outcomes challenging. In contrast, mouse models provide an experimental control precision, which facilitates analyses mechanistic studies role on infection. Here we use mapping cross between two distinct Collaborative Cross strains with respect SARS-CoV disease outcomes. We find several loci differential outcome for traits in context Importantly, identify locus Chromosome 9 that shows conserved synteny GWAS SARS-CoV-2 severe disease. follow-up confirm this locus, candidate genes,