Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility

Wang, Fang1; Huang, Shujia2,3; Gao, Rongsui1; Zhou, Yuwen2,4; Lai, Changxiang1; Li, Zhichao2,4; Xian, Wenjie1; Qian, Xiaobo2,4; Li, Zhiyu1; Huang, Yushan2,4; Tang, Qiyuan1; Liu, Panhong2,4; Chen, Ruikun1; Liu, Rong2; Li, Xuan1; Tong, Xin2; Zhou, Xuan1; Bai, Yong2; Duan, Gang1; Zhang, Tao2; Xu, Xun2,5; Wang, Jian2,6; Yang, Huanming2,6; Liu, Siyang2; He, Qing1; Jin, Xin2,3; Liu, Lei1

2020-11-10

10.1038/s41421-020-00231-4

Cell Discovery   影响因子和分区

2056-5968

2056-5968

The COVID-19 pandemic has accounted for millions of infections and hundreds of thousand deaths worldwide in a short-time period. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed interindividual phenotypic variability. Here, we report the first host genetic study in the Chinese population by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe, and critical ill patients after the correction of potential confounding factors. Pedigree analysis suggested a potential monogenic effect of loss of function variants in GOLGA3 and DPP7 for critically ill and asymptomatic disease demonstration. Genome-wide association study suggests the most significant gene locus associated with severity were located in TMEM189-UBE2V1 that involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We identified that the HLA-A*11:01, B*51:01, and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial genomic study of Chinese patients provides genetic insights into the phenotypic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China[31900487] ; Guangdong Provincial Key Laboratory of Genome Read and Write[2017B030301011]

Cell Biology

Cell Biology

WOS:000588712300001

SPRINGERNATURE

Web of Science

1.Southern Univ Sci & Technol, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis, Peoples Hosp Shenzhen 3, Shenzhen 518112, Guangdong, Peoples R China
2.BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China
3.South China Univ Technol, Sch Med, Guangzhou 510006, Guangdong, Peoples R China
4.Univ Chinese Acad Sci, BGI Educ Ctr, Shenzhen 518083, Guangdong, Peoples R China
5.BGI Shenzhen, Guangdong Prov Key Lab Genome Read & Write, Shenzhen 518120, Guangdong, Peoples R China
6.James D Watson Inst Genome Sci, Hangzhou 310008, Zhejiang, Peoples R China

Wang, Fang,Huang, Shujia,Gao, Rongsui,et al. Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility[J]. Cell Discovery,2020,6(1).

Wang, Fang.,Huang, Shujia.,Gao, Rongsui.,Zhou, Yuwen.,Lai, Changxiang.,...&Liu, Lei.(2020).Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility.Cell Discovery,6(1).

Wang, Fang,et al."Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility".Cell Discovery 6.1(2020).