Zhu Huanhuan, Zheng Fang, Li Linxuan, Jin Yan, Luo Yuxue, Li Zhen, Zeng Jingyu, Tang Ling, Li Zilong, Xia Ningyu, Liu Panhong, Han Dan, Shan Ying, Zhu Xiaoying, Liu Siyang, Xie Rong, Chen Yilin, Liu Wen, Liu Longqi, Xu Xun, Wang Jian, Yang Huanming, Shen Xia, Jin Xin, Cheng Fanjun
BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
iScience. 2021 Oct 22;24(10):103186. doi: 10.1016/j.isci.2021.103186. Epub 2021 Sep 30.
The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes complex and , respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including and . We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.
新冠疫情已在全球造成超过2.2亿人感染，450万人死亡。目前的风险因素无法完全解释疾病严重程度的多样性。在此，我们对大量患者的实验室检查和临床评估进行了全面分析，以研究基因对新冠严重程度的影响。通过进行全基因组关联研究（GWAS）分析，我们发现了几个与实验室指标的具体关联，并使用孟德尔随机化（MR）分析进一步研究这些指标对疾病严重程度的因果关系。基于MR研究确定了两个因果指标，即白细胞计数和胆固醇水平，其功能基因分别位于基因复合体和。我们基于基因的分析和基因集富集分析（GSEA）揭示了四条干扰素通路，包括和。我们希望我们的工作将有助于研究疾病的遗传机制，并为新冠诊断和治疗提供有用的参考。
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