Abstract
Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment. In the last few years great advances have been made in dissecting the genetic basis of JIA with now 17 confirmed susceptibility loci identified. One of these loci, the MHC region, has been established for many years but the complexity and the broad linkage disequilibrium (LD) across the region has rendered fine-mapping associations challenging. Novel imputation strategies can now be utilized to impute HLA classical alleles and amino acids across the region.
Highlights
Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment
The most significant association across the HLA region was for the phenylalanine residue at amino acid 67 of HLA-DRB1, OR = 3.03, p = 1 x 10-179
The omnibus test for all amino acids across HLA-DRB1 showed most significant association at HLA-DRB1 amino acid 13 and conditioning on all residues at amino acid 13 found significant association remaining at HLA-DRB1 amino acid 67, suggesting two independent effects in HLA-DRB1
Summary
Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment. In the last few years great advances have been made in dissecting the genetic basis of JIA with 17 confirmed susceptibility loci identified. One of these loci, the MHC region, has been established for many years but the complexity and the broad linkage disequilibrium (LD) across the region has rendered fine-mapping associations challenging. Novel imputation strategies can be utilized to impute HLA classical alleles and amino acids across the region
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