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Annu Rev Biomed Data Sci
. 2023 May 17.
doi: 10.1146/annurev-biodatasci-020222-021705. Online ahead of print. Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants
Aurélie Cobat 1 2 3 , Qian Zhang 1 2 3 , Covid Human Genetic Effort 1 , Laurent Abel 1 2 3 , Jean-Laurent Casanova 1 2 3 4 5 , Jacques Fellay 6 7 8
Affiliations
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 6 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
. 2023 May 17.
doi: 10.1146/annurev-biodatasci-020222-021705. Online ahead of print. Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants
Aurélie Cobat 1 2 3 , Qian Zhang 1 2 3 , Covid Human Genetic Effort 1 , Laurent Abel 1 2 3 , Jean-Laurent Casanova 1 2 3 4 5 , Jacques Fellay 6 7 8
Affiliations
- PMID: 37196358
- DOI: 10.1146/annurev-biodatasci-020222-021705
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 6 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.