Initial Whole Genome Sequencing and Analysis of the Host Genetic Contribution to COVID-19 Severity and Susceptibility

摘要: The COVID-19 pandemic has accounted for more than five million infections and hundreds of thousand deaths worldwide in the past six months. patients demonstrate a great diversity clinical laboratory manifestations disease severity. Nonetheless, little is known about host genetic contribution to observed inter-individual phenotypic variability. Here, we report first study China by deeply sequencing analyzing 332 categorized varying levels severity from Shenzhen Third People9s Hospital. Based on total 22.2 variants, conducted both single-variant gene-based association tests among groups including asymptomatic, mild, moderate, severe critical ill after correction potential confounding factors. most significant gene loci associated with located TMEM189-UBE2V1 involved IL-1 signaling pathway. p.Val197Met missense variant that affects stability TMPRSS2 protein displays decreasing allele frequency compared mild general population. We also identified HLA-A*11:01, B*51:01 C*14:02 alleles significantly predispose worst outcome patients. This initial Chinese provides comprehensive view difference patient highlighted genes variants may help guide targeted efforts containing outbreak. Limitations advantages were reviewed future international elucidating architecture host-pathogen interaction other infectious complex diseases.