Insights into genetic factors contributing to variability in SARS-CoV-2 susceptibility and COVID-19 disease severity

Matteo D’Antonio; Jennifer Nguyen; Timothy D. Arthur; Hiroko Matsui; Agnieszka D’Antonio‐Chronowska; Kelly A. Frazer; Benjamin M. Neale; Mark J. Daly; Andrea Ganna; Christine R. Stevens; G. K. Pathak; Shea J. Andrews; Masahiro Kanai; Mattia Cordioli; Juha M Karjalainen; Renato A Polimanti; Matti Pirinen; Nadia V. Harerimana; Kumar Veerapen; Brooke Wolford; Huy Nguyen; Matthew Solomonson; Rachel G. Liao; Karolina Chwiałkowska; Amy Trankiem; Mary K. Balaconis; Caroline Hayward; Anne Richmond; Archie I Campbell; Marcela Morris

doi:10.1016/j.celrep.2021.110020

Genetic & Genomic MedicineCell ReportsNov 1, 2021

Peer-reviewed journal article

Insights into genetic factors contributing to variability in SARS-CoV-2 susceptibility and COVID-19 disease severity

Matteo D’Antonio iD, Jennifer Nguyen iD, Timothy D. Arthur iD, Hiroko Matsui, Agnieszka D’Antonio‐Chronowska iD, Kelly A. Frazer iD, Benjamin M. Neale iD, Mark J. Daly iD, Andrea Ganna iD, Christine R. Stevens iD, G. K. Pathak iD, Shea J. Andrews iD, Masahiro Kanai iD, Mattia Cordioli iD, Juha M Karjalainen iD, Renato A Polimanti iD, Matti Pirinen iD, Nadia V. Harerimana iD, Kumar Veerapen iD, Brooke Wolford iD, Huy Nguyen, Matthew Solomonson iD, Rachel G. Liao iD, Karolina Chwiałkowska iD, Amy Trankiem, , Rasoul Aliannejad iD

Abstract

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we applied colocalization to compare summary statistics for 16 GWASs from the COVID-19 Host Genetics Initiative to investigate similarities and differences in their genetic signals. We identified 9 loci associated with susceptibility (one with two independent GWAS signals; one with an ethnicity-specific signal), 14 associated with severity (one with two independent GWAS signals; two with ethnicity-specific signals) and one harboring two discrepant GWAS signals (one for susceptibility; one for severity). Utilizing colocalization we also identified 45 GTEx tissues that had eQTL(s) for 18 genes strongly associated with GWAS signals in eleven loci (1-4 genes per locus). Some of these genes showed tissue-specific altered expression and others showed altered expression in up to 41 different tissue types. Our study provides insights into the complex molecular mechanisms underlying inherited predispositions to COVID-19-disease phenotypes.

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