Photo Credit: wildpixel

The following is a summary of “Cross-trait GWAS in COVID-19 and systemic sclerosis reveals novel genes implicated in fibrotic and inflammation pathways,” published in the January 2025 issue of Rheumatology by Rosa-Baez et al. 

COVID-19 and systemic sclerosis (SSc) share clinical similarities, immune response alterations, and therapeutic options. A common genetic component has also been identified in other immune-mediated inflammatory diseases. 

Researchers conducted a retrospective study to evaluate the shared genetic architecture between COVID-19 and SSc. 

They retrieved genomic data from 2 European-ancestry cohorts: 2,597,856 individuals from the COVID-19 Host Genetics Initiative consortium and 26,679 individuals from the largest genomic scan in SSc. They performed cross-trait meta-analyses, including over 9.3 million SNPs, conducted functional annotation to prioritize potential causal genes, and performed drug repurposing analysis. 

The results showed 19 non-HLA pleiotropic loci, including 2 novel associations (BMP1 and PPARG) and 12 new shared loci. Functional annotation highlighted potential regulatory roles and identified causal genes involved in fibrotic and inflammatory pathways. An antagonistic pleiotropy model of IFN signalling was observed between COVID-19 and SSc, with the TYK2 P1104A missense variant showing a protective effect for SSc and a risk factor for COVID-19, along with 2 additional novel pleiotropic associations (IRF8 and SENP7). The findings suggest new therapeutic options for both conditions. 

Investigators confirmed the genetic resemblance between COVID-19 and SSc, revealing a common genetic contribution affecting fibrotic and immune pathways. 

Source: academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keaf028/7989306