Juvenile idiopathic arthritis shares 84 genetic regions with adult rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, with the Janus kinase-signal transducers and activators of transcription pathway playing a key role, according to a recent study published in JAMA Network Open.
Researchers conducted a comprehensive genetic association study to investigate the connections between JIA and adult rheumatic diseases. The analysis included data from 33,207 participants across four cohorts, focusing on identifying shared genetic regions and pathways that influence the progression from juvenile idiopathic arthritis (JIA) to adult conditions.
The meta-analyzed JIA cohort included 4,550 cases (1,485 from the U.S., Australia, and Norway, and 3,305 from the U.K.) and 18,446 controls. Participants were predominantly of European ancestry. Researchers used genome-wide association studies (GWAS) to identify genetic correlations, supported by advanced statistical techniques such as genetic correlation analysis, colocalization, and Mendelian randomization (MR). Analyses were performed between September 2023 and April 2024.
The study identified 84 genomic regions with signals shared across diseases, including 20 loci common to JIA and adult rheumatic conditions. Notable discoveries included novel loci near the IL12A-AS1 and IRF5 genes. Pathway analysis revealed that the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway is central to the pathogenesis of these diseases.
MR analyses identified associations between 11 proteins and rheumatic conditions, including interleukin-27, ICAM5, and TIMP4, highlighting the role of protein-level insights in understanding genetic contributions. A genetic risk score (GRS) model, built from 27 shared genomic regions, showed that JIA patients had a significantly higher GRS (0.96; 95% CI, 0.95–0.97) than controls (0.89; 95% CI, 0.89–0.90; P = 2.19 × 10⁻³⁹), indicating an elevated risk of arthritis persisting into adulthood.
These findings underscore the potential for a genomics-based approach to refining JIA classifications and exploring therapeutic strategies. The overlap in pathogenic mechanisms, particularly through the JAK-STAT pathway, suggests opportunities to repurpose treatments effective in adult rheumatic diseases for pediatric patients. However, the study's limitations—such as the lack of longitudinal data and diverse populations—call for further research to validate these insights.
Full disclosures and methodology details are available in the original study.