Integrative genomics analysis reveals a 21q22.11 locus contributing risk to COVID-19.
Hum Mol Genet
; 30(13): 1247-1258, 2021 06 17.
Article
em En
| MEDLINE
| ID: mdl-33949668
ABSTRACT
The systematic identification of host genetic risk factors is essential for the understanding and treatment of coronavirus disease 2019 (COVID-19). By performing a meta-analysis of two independent genome-wide association summary datasets (N = 680 128), a novel locus at 21q22.11 was identified to be associated with COVID-19 infection (rs9976829 in IFNAR2-IL10RB, odds ratio = 1.16, 95% confidence interval = 1.09-1.23, P = 2.57 × 10-6). The rs9976829 represents a strong splicing quantitative trait locus for both IFNAR2 and IL10RB genes, especially in lung tissue (P = 1.8 × 10-24). Integrative genomics analysis of combining genome-wide association study with expression quantitative trait locus data showed the expression variations of IFNAR2 and IL10RB have prominent effects on COVID-19 in various types of tissues, especially in lung tissue. The majority of IFNAR2-expressing cells were dendritic cells (40%) and plasmacytoid dendritic cells (38.5%), and IL10RB-expressing cells were mainly nonclassical monocytes (29.6%). IFNAR2 and IL10RB are targeted by several interferons-related drugs. Together, our results uncover 21q22.11 as a novel susceptibility locus for COVID-19, in which individuals with G alleles of rs9976829 have a higher probability of COVID-19 susceptibility than those with non-G alleles.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 21
/
Receptor de Interferon alfa e beta
/
Subunidade beta de Receptor de Interleucina-10
/
COVID-19
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China