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Genetic correlations, shared risk genes and immunity landscapes between COVID-19 and venous thromboembolism: evidence

Langchao Yan1, Shifu Li2,3, Qian Hu4

  • 1Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University, No. 161, West 5th Road, Xincheng District, Xi'an, 710003, Shanxi, China.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|March 3, 2024
PubMed

Insights

This study reveals genetic links between COVID-19 and venous thromboembolism (VTE), identifying TP53I3 and SLPI as key genes. These findings offer potential therapeutic targets for managing both conditions concurrently.

Area of Science:

  • Genetics
  • Immunology
  • Bioinformatics

Background:

  • Patients with coronavirus disease 2019 (COVID-19) face increased risk of venous thromboembolism (VTE).
  • The genetic underpinnings and shared genes between COVID-19 and VTE remain poorly understood.
  • Understanding these connections is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate genetic correlations between COVID-19 and VTE.
  • To identify common pathogenic mechanisms and shared genes underlying both diseases.
  • To explore potential therapeutic targets for simultaneous treatment.

Main Methods:

  • Utilized linkage disequilibrium score (LDSC) regression and Mendelian Randomization (MR) analysis for genetic association and causal effect studies.
  • Employed bioinformatics and systems biology approaches, including WGCNA and single-cell transcriptome sequencing, on public datasets (GEO).
  • Constructed miRNA-gene and transcription factor-gene interaction networks and analyzed epigenetic data (ATAC-seq, Chip-seq).

Main Results:

  • Confirmed positive genetic correlations between COVID-19 and VTE.
  • Identified 26 potential shared genes, with TP53I3 and SLPI highlighted as upregulated hub genes with diagnostic value.
  • Revealed immune process alterations, including downregulation of effector memory CD8+ T cells and activated B cells, with hub genes predominantly expressed in monocytes.

Conclusions:

  • Established significant genetic correlations between COVID-19 and VTE.
  • Pinpointed TP53I3 and SLPI as crucial hub genes potentially linking the severity of both conditions.
  • Identified common regulators (miRNAs and TFs) suggesting opportunities for combined therapeutic strategies.
Abstract

Keywords:
COVID-19Gene-regulatory networksGenetic correlationHub geneImmunity landscapesVenous thromboembolism

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