An amino acid motif in HLA-DRß1 distinguishes patients with uveitis in juvenile idiopathic arthritis

A.J.W. Haasnoot; M.W. Schilham; S.S.M. Kamphuis; P.C.E. Hissink Muller; A. Heiligenhaus; D. Foell; R.A. Ophoff; T.R.D.J. Radstake; A.I. Den Hollander; T.H.C.M. Reinards; S. Hiddingh; N. Schalij-Delfos; E.P.A.H. Hoppenreijs; M.A.J. van Rossum; C. Wouters; R.K. Saurenmann; N. Wulffraat; R. ten Cate; J.H. de Boer; S.L. Pulit; J.J.W. Kuiper

We performed our analysis in two phases that we then jointly analyzed to improve power for locus discovery. 21 In Phase 1, we genotyped 137 JIA-associated uveitis cases, 247 nonuveitis JIA samples, and 398 population-level controls without JIA or uveitis, all collected from within the Netherlands. Samples were genotyped on the HumanOmniExpress24 array, containing ~700,000 markers. Samples and SNPs underwent quality control (QC) (Materials and Methods) to remove those samples and SNPs with low-quality genotyping data. After QC, 126 JIA-associated uveitis cases, 231 non-uveitis JIA samples, and 394 population-level controls remained ( Table 1) . We prephased the genotyping data using SHAPEIT2 [22] [23] [24] and imputed the phased haplotypes with IMPUTE2, 25-27 using a reference panel constructed from the 2,504 global samples included in the 1000 Genomes Project Phase 3. 28 In parallel to genome-wide imputation, we extracted the MHC from the genotype data and imputed additional SNPs, amino acids and HLA types using the SNP2HLA pipeline 29 (Materials and Methods).