HLA-DRB1*11 and regulatory variants of the class II MHC locus are strong risk factors for systemic juvenile idiopathic arthritis

Authors

• MJ Ombrello
• EF Remmers
• DL Kastner
• on behalf of INCHARGE Consortium

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is a potentially life-threatening childhood inflammatory disease whose pathophysiology is poorly understood. To determine whether genetic variation within the major histocompatibility complex (MHC) locus influenced sJIA susceptibility, we performed a regional association study in children with sJIA from 9 countries. We determined single nucleotide polymorphism (SNP) genotypes in 982 children with sJIA and 431 healthy subjects, and combined the genotype data with in silico SNP data from 7579 additional healthy subjects. The dataset was divided into 9 case-control strata by country of origin. SNP and HLA type imputation and association testing were performed in each stratum, and the association results were meta-analyzed. To determine the regulatory capacity of sJIA-associated SNPs, we examined datasets from the ENCODE and NIH Roadmap Epigenome Projects. The strongest sJIA-associated SNP, rs151043342 (p=7E-15, OR 2.2 [1.8,2.7]), was part of a cluster of 886 sJIA-associated SNPs (p

Scientific Focus Area: Genetics and Genomics

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