Schmiedel Benjamin J, Rocha Job, Gonzalez-Colin Cristian, Bhattacharyya Sourya, Madrigal Ariel, Ottensmeier Christian H, Ay Ferhat, Chandra Vivek, Vijayanand Pandurangan
La Jolla Institute for Immunology, La Jolla, CA, USA.
Center for Genomic Sciences, National Autonomous University of Mexico, Cuernavaca, Morelos, Mexico.
Nat Commun. 2021 Nov 19;12(1):6760. doi: 10.1038/s41467-021-26888-3.
Common genetic polymorphisms associated with COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Given the importance of immune cells in the pathogenesis of COVID-19 illness, here we assessed the effects of COVID-19-risk variants on gene expression in a wide range of immune cell types. Transcriptome-wide association study and colocalization analysis revealed putative causal genes and the specific immune cell types where gene expression is most influenced by COVID-19-risk variants. Notable examples include OAS1 in non-classical monocytes, DTX1 in B cells, IL10RB in NK cells, CXCR6 in follicular helper T cells, CCR9 in regulatory T cells and ARL17A in T2 cells. By analysis of transposase accessible chromatin and H3K27ac-based chromatin-interaction maps of immune cell types, we prioritized potentially functional COVID-19-risk variants. Our study highlights the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations.
与新冠病毒疾病相关的常见基因多态性可用于发现驱动疾病发病机制的分子途径和细胞类型。鉴于免疫细胞在新冠病毒疾病发病机制中的重要性，我们在此评估了新冠病毒风险变异对多种免疫细胞类型中基因表达的影响。全转录组关联研究和共定位分析揭示了推定的因果基因以及基因表达受新冠病毒风险变异影响最大的特定免疫细胞类型。显著的例子包括非经典单核细胞中的OAS1、B细胞中的DTX1、自然杀伤细胞中的IL10RB、滤泡辅助性T细胞中的CXCR6、调节性T细胞中的CCR9以及T2细胞中的ARL17A。通过分析免疫细胞类型的转座酶可及染色质和基于H3K27ac的染色质相互作用图谱，我们对潜在功能性新冠病毒风险变异进行了优先级排序。我们的研究突出了新冠病毒遗传风险变异影响多种免疫细胞类型功能并影响严重疾病表现的潜力。
