Phenome-wide and expression quantitative trait locus associations of coronavirus disease 2019 genetic risk loci
Chang Yoon Moon,
Brian M. Schilder,
Towfique Raj,
Kuan-lin Huang
Affiliations
Chang Yoon Moon
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Brian M. Schilder
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience & Friedman Brain Institute, New York, NY, USA; Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Towfique Raj
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience & Friedman Brain Institute, New York, NY, USA; Ronald M. Loeb Center for Alzheimer's disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Kuan-lin Huang
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Corresponding author
Summary: While several genes and clinical traits have been associated with higher risk of severe coronavirus disease 2019 (COVID-19), how host genetic variants may interact with these parameters and contribute to severe disease is still unclear. Herein, we performed phenome-wide association study, tissue and immune-cell-specific expression quantitative trait locus (eQTL)/splicing quantitative trait locus, and colocalization analyses for genetic risk loci suggestively associated with severe COVID-19 with respiratory failure. Thirteen phenotypes/traits were associated with the severe COVID-19-associated loci at the genome-wide significance threshold, including monocyte counts, fat metabolism traits, and fibrotic idiopathic interstitial pneumonia. In addition, we identified tissue and immune subtype-specific eQTL associations affecting 48 genes, including several ones that may directly impact host immune responses, colocalized with the severe COVID-19 genome-wide association study associations, and showed altered expression in single-cell transcriptomes. Collectively, our work demonstrates that host genetic variations associated with multiple genes and traits show genetic pleiotropy with severe COVID-19 and may inform disease etiology.
