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10.1007/s00439-021-02305-z

http://scihub22266oqcxt.onion/10.1007/s00439-021-02305-z
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suck abstract from ncbi


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pmid34155559      Hum+Genet 2021 ; 140 (9): 1313-1328
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  • Association of CXCR6 with COVID-19 severity: delineating the host genetic factors in transcriptomic regulation #MMPMID34155559
  • Dai Y; Wang J; Jeong HH; Chen W; Jia P; Zhao Z
  • Hum Genet 2021[Sep]; 140 (9): 1313-1328 PMID34155559show ga
  • The coronavirus disease 2019 (COVID-19) is an infectious disease that mainly affects the host respiratory system with ~ 80% asymptomatic or mild cases and ~ 5% severe cases. Recent genome-wide association studies (GWAS) have identified several genetic loci associated with the severe COVID-19 symptoms. Delineating the genetic variants and genes is important for better understanding its biological mechanisms. We implemented integrative approaches, including transcriptome-wide association studies (TWAS), colocalization analysis, and functional element prediction analysis, to interpret the genetic risks using two independent GWAS datasets in lung and immune cells. To understand the context-specific molecular alteration, we further performed deep learning-based single-cell transcriptomic analyses on a bronchoalveolar lavage fluid (BALF) dataset from moderate and severe COVID-19 patients. We discovered and replicated the genetically regulated expression of CXCR6 and CCR9 genes. These two genes have a protective effect on lung, and a risk effect on whole blood, respectively. The colocalization analysis of GWAS and cis-expression quantitative trait loci highlighted the regulatory effect on CXCR6 expression in lung and immune cells. In the lung-resident memory CD8(+) T (T(RM)) cells, we found a 2.24-fold decrease of cell proportion among CD8(+) T cells and lower expression of CXCR6 in the severe patients than moderate patients. Pro-inflammatory transcriptional programs were highlighted in the T(RM) cellular trajectory from moderate to severe patients. CXCR6 from the 3p21.31 locus is associated with severe COVID-19. CXCR6 tends to have a lower expression in lung T(RM) cells of severe patients, which aligns with the protective effect of CXCR6 from TWAS analysis.
  • |*COVID-19/genetics/immunology[MESH]
  • |*Receptors, CXCR6/genetics/immunology[MESH]
  • |CD8-Positive T-Lymphocytes/*immunology[MESH]
  • |Female[MESH]
  • |Genome-Wide Association Study[MESH]
  • |Humans[MESH]
  • |Immunologic Memory/*genetics[MESH]
  • |Lung/*immunology/virology[MESH]
  • |Male[MESH]
  • |Quantitative Trait Loci/*immunology[MESH]
  • |Receptors, CCR/genetics/immunology[MESH]
  • |Risk Factors[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Severity of Illness Index[MESH]


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