Genome-wide association study of 24 paediatric-onset immune-mediated inflammatory diseases (IMIDs) — including juvenile idiopathic arthritis and related rheumatic diseases — in 18,086 cases and 131,019 European-ancestry controls, examining shared and disease-specific genetic architecture, comparison with adult IMIDs, and drug-target prioritisation.
SNP-based heritability ranged from 28.9% (allergic) to 61.9% (autoimmune IMIDs). Meta-analysis found 39 genome-wide significant non-MHC loci (15 novel); 19 were shared across categories. Priority Index analysis flagged 178 high-scoring genes, 43 of which are approved or investigational IMID drug targets. Core pathways included NF-κB, JAK-STAT, Th17, PD-1/PD-L1, CTLA-4, and osteoclast differentiation.
Analysis restricted to European ancestry, limiting generalisability. Study relies on cross-disease GWAS meta-analysis with heterogeneous phenotype definitions across 24 conditions. Drug-target prioritisation is genomic and computational — functional or clinical validation is not yet provided.
Paediatric IMIDs share core immune pathways (JAK-STAT, NF-κB, CTLA-4) with adult rheumatic diseases, supporting the rationale for trialling adult-approved biologics and targeted therapies in children. Clinicians can expect genomic tools to increasingly inform classification and precision treatment selection in paediatric rheumatology.
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