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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

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Cross-trait GWAS in COVID-19 and systemic sclerosis reveals novel genes implicated in fibrotic and inflammation

Carlos Rosa-Baez1, Gonzalo Borrego-Yaniz1, Inmaculada Rodriguez-Martin1

  • 1Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.

Rheumatology (Oxford, England)
|January 29, 2025
PubMed

Insights

This study reveals shared genetic factors between COVID-19 and systemic sclerosis (SSc), highlighting common immune and fibrotic pathways. Findings suggest potential new therapeutic targets for both conditions.

Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • Coronavirus disease 2019 (COVID-19) and systemic sclerosis (SSc) exhibit overlapping clinical features, immune responses, and treatments.
  • These similarities suggest a potential shared genetic basis, as observed in other immune-mediated inflammatory diseases.

Purpose of the Study:

  • To investigate the shared genetic architecture between COVID-19 and SSc for the first time.
  • To identify common genetic variants influencing susceptibility and severity in both diseases.

Main Methods:

  • Utilized genomic data from large European cohorts for COVID-19 (n=2,597,856) and SSc (n=26,679).
  • Performed cross-trait meta-analyses of over 9.3 million single nucleotide polymorphisms (SNPs).
  • Conducted functional annotation and drug repurposing analyses to identify causal genes and therapeutic strategies.

Main Results:

  • Identified 19 non-HLA pleiotropic loci, including novel associations (BMP1, PPARG) and 12 new shared loci.
  • Functional annotation highlighted regulatory roles and implicated genes in fibrotic and inflammatory pathways.
  • Observed antagonistic pleiotropy in IFN signaling, with the TYK2 P1104A variant showing differential effects in SSc and COVID-19, alongside novel pleiotropic associations (IRF8, SENP7).

Conclusions:

  • Confirmed genetic resemblance between COVID-19 susceptibility/severity and SSc.
  • Revealed a novel common genetic contribution impacting fibrotic and immune pathways.
  • Identified potential therapeutic avenues for managing both COVID-19 and SSc.
Abstract

Keywords:
COVID-19fibrosisgeneticsinflammationsystemic sclerosis

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