Exploring COVID-19 causal genes through disease-specific Cis-eQTLs.

Abstract

Genome-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.

• Authors: Sainan Zhang, Ping Wang, Lei Shi, Chao Wang, Zijun Zhu, Changlu Qi, Yubin Xie, Shuofeng Yuan, Liang Cheng, Xin Yin, Xue Zhang
• Journal: Virus research (Virus Res) Vol. 342 Pg. 199341 (04 2024) ISSN: 1872-7492 [Electronic] Netherlands
• PMID: 38403000 (Publication Type: Journal Article)
• Copyright: Copyright © 2024. Published by Elsevier B.V.

Chemical References

• RNA, Small Interfering

Topics

• Humans
• Genome-Wide Association Study
• COVID-19
• SARS-CoV-2 (genetics)
• RNA, Small Interfering
• RNA-Seq