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10.1093/hmg/ddab125

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33949668!8136003!33949668
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suck abstract from ncbi


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pmid33949668      Hum+Mol+Genet 2021 ; 30 (13): 1247-1258
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  • Integrative genomics analysis reveals a 21q22 11 locus contributing risk to COVID-19 #MMPMID33949668
  • Ma Y; Huang Y; Zhao S; Yao Y; Zhang Y; Qu J; Wu N; Su J
  • Hum Mol Genet 2021[Jun]; 30 (13): 1247-1258 PMID33949668show ga
  • 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 x 10-6). The rs9976829 represents a strong splicing quantitative trait locus for both IFNAR2 and IL10RB genes, especially in lung tissue (P = 1.8 x 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.
  • |*Chromosomes, Human, Pair 21[MESH]
  • |Alleles[MESH]
  • |Antiviral Agents/pharmacology[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19/*genetics/immunology[MESH]
  • |Cytokines/genetics[MESH]
  • |Genetic Predisposition to Disease[MESH]
  • |Genome-Wide Association Study[MESH]
  • |Genomics/methods[MESH]
  • |Humans[MESH]
  • |Interleukin-10 Receptor beta Subunit/*genetics[MESH]
  • |Molecular Targeted Therapy[MESH]
  • |Polymorphism, Single Nucleotide[MESH]
  • |Quantitative Trait Loci[MESH]


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