iScience (Oct 2021)
A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity
- Huanhuan Zhu,
- Fang Zheng,
- Linxuan Li,
- Yan Jin,
- Yuxue Luo,
- Zhen Li,
- Jingyu Zeng,
- Ling Tang,
- Zilong Li,
- Ningyu Xia,
- Panhong Liu,
- Dan Han,
- Ying Shan,
- Xiaoying Zhu,
- Siyang Liu,
- Rong Xie,
- Yilin Chen,
- Wen Liu,
- Longqi Liu,
- Xun Xu,
- Jian Wang,
- Huanming Yang,
- Xia Shen,
- Xin Jin,
- Fanjun Cheng
Affiliations
- Huanhuan Zhu
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China
- Fang Zheng
- Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Linxuan Li
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
- Yan Jin
- Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Yuxue Luo
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China
- Zhen Li
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Jingyu Zeng
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; College of Innovation and Experiment, Northwest A&F University, Yangling, Shaanxi 712100, China
- Ling Tang
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Zilong Li
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China
- Ningyu Xia
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Panhong Liu
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
- Dan Han
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Ying Shan
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China
- Xiaoying Zhu
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Siyang Liu
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong 510006, China
- Rong Xie
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Yilin Chen
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Wen Liu
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Longqi Liu
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China
- Xun Xu
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, Guangdong 518120, China
- Jian Wang
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; James D. Watson Institute of Genome Science, Hangzhou, Zhejiang 310008, China
- Huanming Yang
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; James D. Watson Institute of Genome Science, Hangzhou, Zhejiang 310008, China
- Xia Shen
- Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
- Xin Jin
- BGI-Shenzhen, Shenzhen, Guangdong 518083, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China; Corresponding author
- Fanjun Cheng
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 10
p. 103186
Abstract
Summary: 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 MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. 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.
