Integrative genomics analysis reveals a 21q22.11 locus contributing risk to COVID-19.
Hum Mol Genet
; 30(13): 1247-1258, 2021 06 17.
Article
in English
| MEDLINE | ID: covidwho-1216653
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Chromosomes, Human, Pair 21
/
Receptor, Interferon alpha-beta
/
Interleukin-10 Receptor beta Subunit
/
COVID-19
Type of study:
Prognostic study
/
Reviews
/
Systematic review/Meta Analysis
Limits:
Humans
Language:
English
Journal:
Hum Mol Genet
Journal subject:
Molecular Biology
/
Genetics, Medical
Year:
2021
Document Type:
Article
Affiliation country:
Hmg
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