medRxiv : the preprint server for health sciences · 2026
Identification and evaluation of 41 risk loci for juvenile idiopathic arthritis informs precision medicine: mechanistic implications of DNA topology and an HLA-A*02:01-ERAP2 interaction.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Ainsworth Hannah C, Khvatkova Ekaterina S, Sudman Marc, Marion Miranda C, Jiang Kaiyu, Bohnsack John F, Comeau Mary E, Gaffney Patrick M, Haas Johannes-Peter, Howard Timothy D, Hyrich Kimme, James Judith A, Nigrovic Peter A, Nordal Ellen B, Rosenberg Alan M, Rygg Marite, Smith Samantha L, Videm Vibeke, Wedderburn Lucy R, Wise Carol A, Yeung Rae S M, Thompson Susan D, Schulert Grant S, Prahalad Sampath, Bowes John, Angeles-Han Sheila T, Jarvis James N, Langefeld Carl D
Аннотация
Juvenile idiopathic arthritis (JIA), the most common class of pediatric rheumatic diseases, can lead to joint damage and extra-articular features including uveitis. Early treatment can improve functional outcomes; but many patients do not respond to first-line treatments. We present a JIA Immunochip-based association analysis of rheumatoid factor-negative polyarticular JIA and oligoarticular JIA. This study spans 3,939 cases and 14,412 controls, including 1,123 cases and 1,356 controls not previously analyzed. We identify 41 (14 novel) JIA risk regions and report a JIA polygenic risk score that also associates with age of onset. Functional mechanisms presented include: a novel interaction between HLA-A*02:01 and ERAP2 , cluster-based approach for functional amino acid discovery within HLA-DRB1, and sequence-dependent DNA topology for variant prioritization. We present a comprehensive list of curated gene-drug/small molecule interactions for clinically focused studies. These findings provide a deepened understanding of the genetics of JIA and potential mechanisms to inform precision medicine.