Exploring COVID-19 Causal Genes through Disease-specific Cis-eQTLs

Virus Res. 2024 Feb 23:199341. doi: 10.1016/j.virusres.2024.199341. Online ahead of print.ABSTRACTGenome-wide association study (GWAS) analysis has exposed that genetic factors play important roles in COVID-19. Whereas a deeper understanding of the underlying mechanism of COVID-19 was hindered by the lack of expression of quantitative trait loci (eQTL) data specific for disease. To this end, we identified COVID-19-specific cis-eQTLs by integrating nucleotide sequence variations and RNA-Seq data from COVID-19 samples. These identified eQTLs have different regulatory effect on genes between patients and controls, indicating that SARS-CoV-2 infection may cause alterations in the human body's internal environment. Individuals with the TT genotype in the rs1128320 region seemed more susceptible to SARS-CoV-2 infection and developed into severe COVID-19 due to the abnormal expression of IFITM1. We subsequently discovered potential causal genes, of the result, a total of 48 genes from six tissues were identified. siRNA-mediated depletion assays in SARS-CoV-2 infection proved that 14 causal genes were directly associated with SARS-CoV-2 infection. These results enriched existing research on COVID-19 causal genes and provided a new sight in the mechanism exploration for COVID-19.PMID:38403000 | DOI:10.1016/j.virusres.2024.199341
Source: Virus Research - Category: Virology Authors: Source Type: research