Cross-Trait Meta-Analysis Reveals a Genetic Link between Inflammation and Aging in Giant Cell Arteritis
Laura Martínez-Gutiérrez1, Inmaculada Rodriguez-Martin1, Gonzalo Borrego-Yaniz1
1Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
Aging and Disease
|September 3, 2025
Summary
Giant cell arteritis (GCA) shares genetic links with aging markers like telomere shortening and epigenetic age acceleration. This study identifies new genetic loci and potential therapies targeting inflammation and cellular senescence in GCA.
Area of Science:
- Genetics
- Immunology
- Gerontology
Background:
- Giant cell arteritis (GCA) is an inflammatory disease strongly associated with aging.
- The precise mechanisms linking aging and GCA susceptibility are not well understood.
- Genetic factors influencing biological aging markers may play a role in GCA development.
Purpose of the Study:
- To investigate the shared genetic basis between GCA and biological aging markers.
- To enhance the understanding of aging's role in GCA pathogenesis.
- To identify potential therapeutic targets for GCA.
Main Methods:
- Meta-analysis of genome-wide association studies (GWASs) for GCA, telomere length, and epigenetic age acceleration (EAA).
- Analysis of approximately 6.6 million genetic variants using ASSET.
- Functional annotation and causal gene prioritization using FUMA.
- Drug repurposing analysis for potential GCA therapies.
Main Results:
- Identified 21 genetic variants shared between GCA and at least one aging marker.
- Confirmed known GCA risk factors PTPN22 and PLG, and identified novel susceptibility loci.
- Prioritized causal genes (e.g., SERPING1, SAR1B) involved in inflammation and senescence.
- Found dysregulated expression of certain genes (e.g., PDE1B, ATXN2) in active GCA patients.
- Highlighted sulfasalazine and NF-κB targeting drugs as potential GCA therapeutics.
Conclusions:
- Significant genetic overlap exists between GCA and aging markers.
- Shared molecular pathways involving inflammation and senescence link aging and GCA.
- Findings provide insights into GCA pathogenesis and suggest novel therapeutic strategies.
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