COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types.
COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types.
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COVID-19 遗传风险变异与不同免疫细胞类型中多个基因的表达相关。
DOI：
10.1101/2020.12.01.407429
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Vijayanand,Pandurangan
中科院分区：
文献类型：
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作者：
Schmiedel,BenjaminJ;Chandra,Vivek;Rocha,Job;Gonzalez-Colin,Cristian;Bhattacharyya,Sourya;Madrigal,Ariel;Ottensmeier,ChristianH;Ay,Ferhat;Vijayanand,Pandurangan
与COVID-19疾病相关的常见遗传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COVID-19疾病发病机制中的重要性，我们在此评估了COVID-19风险变体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致病基因和基因表达最受COVID-19风险变体影响的特定免疫细胞类型。值得注意的例子包括非经典单核细胞中的OAS 1、B细胞中的DTX 1、NK细胞中的IL 10 R、滤泡辅助性T细胞中的CXCR 6、调节性T细胞中的CCR 9和TH 2细胞中的ARL 17 A。通过分析免疫细胞类型的转座酶可及染色质和基于H3 K27 ac的染色质相互作用图谱，我们优先考虑了潜在的功能性COVID-19风险变体。我们的研究强调了COVID-19遗传风险变体影响不同免疫细胞类型功能并影响严重疾病表现的潜力。
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 includeOAS1in non-classical monocytes,DTX1in B cells,IL10RBin NK cells,CXCR6in follicular helper T cells,CCR9in regulatory T cells andARL17Ain TH2 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.