Supplementary Figure 1 Dosage correlation between imputed and genotyped alleles Imputed dosages (0 to 2) of 2-digit alleles (red) and 4-digit alleles (green) of (A) HLA-A, HLA-B, (C) HLA-C, (D) HLA-DQA1, (E) HLA-DQB1, and (F) HLA-DRB1 in 61 East Asian HapMap individuals were compared with the actual dosage (0, 1 or 2). The Pearson's correlation coefficient between the imputed and actual dosages of each allele was plotted according to its allelic frequency. (B)
Supplementary Figure 2 Summary of genome-wide SNP datasets
Supplementary Figure 3 Principal component analysis for Korean subjects. From a principal component (PC) analysis, we obtained the 10 PCs to adjust population stratification in all statistical analysis. The top 2 PCs were used for plotting the result of PC analysis for (A) Korean data only and (B) Korean and HapMap populations (CEU, CHB+JPT, and YRI).
Supplementary Figure 4 Dosage correlation between imputed and genotyped alleles of HLA-DRB1 in study subjects Imputed dosages (0 to 2) of 2-digit alleles (red) and 4-digit alleles (green) of HLA-DRB1 in a subset of the study population (n=1,306) were compared with the actual dosage (0, 1 or 2). The Pearson's correlation coefficient between the imputed and actual dosages of each allele was plotted according to its allelic frequency.
Supplementary Figure 5 Correlation of effect estimates of the amino acid haplotype 11-13-26 between Korean and Japanese. Japanese data was obtained from Furukawa H et al. (PLoS One 2014;9:e87792; Table 1). All classical alleles was recategorized by the amino acid haplotype 11-13-26. Crude ORs were calculated by 2x2 contingency tables according to the presence or absence of haplotypes in cases and controls. The gray line indicates Y=X and green line is a trend line of the data points.
Supplementary Figure 6 Correlation of effect estimates of the amino acid haplotype 11-13-26 between Korean and European European data was obtained from Morris DL et al (Am J Hum Genet 2012;91:778-793). All classical alleles was recategorized by the amino acid haplotype 11-13-26. Because the paper reported only effect estimate of each classical allele, approximate OR was obtained by performing a meta-analysis for the effect estimates of the classical alleles with a same amino acid haplotype. The gray line indicates Y=X and green line is a trend line of the data points.
Supplementary Figure 7 Distinct residue effects at amino acid positions 11 and 13 in systemic lupus erythematosus versus other diseases Each odds ratio of residues at the HLA-DRβ1 amino acid positions 11 and 13 in (A-B) European anti-citrullinated protein autoantibody (ACPA) -positive rheumatoid arthritis (RA), (C-D) Asian ACPA-positive RA, (E-F) European ACPA-negative RA, or (G-H) follicular lymphoma (FL) was plotted against to the odds ratio of the matched residue in systemic lupus erythematosus (SLE). Error bars display their 95% confidence intervals and green lines are trend lines of the data points. There were highly discordant trend between the diseases : discordance P = 1.58 10 104 between European ACPA-positive RA and SLE at position 11; discordance P = 1.92 10 83 between European ACPA-positive RA and SLE at position 13; discordance P = 1.41 10 50 between Asian ACPA-positive RA and SLE at position 11; discordance P = 9.12 10 42 between Asian ACPA-positive RA and SLE at position 13; discordance P = 1.27 10 9 between European ACPA-negative RA and SLE at position 11; discordance P = 4.78 10 8 between European ACPA-negative RA and SLE at position 13. *discordance P values between FL and SLE were not calculated due to lack of raw FL data.
Supplementary Table 1 Concordance rates between genotyped and imputed HLA alleles of 61 CHB+JPT HapMap individuals Reference panel constructed from Korean* Southeast Asian** X X HLA genes European*** Level A B C DRB1 DQA1 DQB1 Mean 2-digit 0.934 0.934 0.992 0.959 NA 0.967 0.957 4-digit 0.910 0.893 0.984 0.893 NA 0.893 0.915 X X X 2-digit 0.967 0.820 0.992 0.975 0.984 1.000 0.956 4-digit 0.885 0.730 0.934 0.861 0.959 0.918 0.881 2-digit 0.992 0.934 1.000 0.984 1.000 1.000 0.985 4-digit 0.910 0.910 0.992 0.943 0.918 0.918 0.932 2-digit 0.984 0.902 1.000 0.992 1.000 1.000 0.980 4-digit 0.934 0.861 0.943 0.902 0.918 0.926 0.914 * Korean HLA reference panel described in Kim K, Bang SY, Lee HS, et al. Construction and Application of a Korean Reference Panel for Imputing Classical Alleles and Amino Acids of Human Leukocyte Antigen Genes. PLoS One 2014; in press. ** Southeast HLA reference panel described in Pillai NE, Okada Y, Saw WY, et al. Predicting HLA alleles from high-resolution SNP data in three Southeast Asian populations. Hum. Mol. Genet. 2014 ; doi: 10.1093/hmg/ddu387. *** European HLA reference panel was described in Jia X, Han B, Onengut-Gumuscu S, et al. Imputing amino acid polymorphisms in human leukocyte antigens. PLoS One 2013; doi: 10.1371/journal.pone.0064683.