HLA Imputation
For each data set, we used SNP2HLA24 to extract SNP genotypes located in the MHC region to impute classical two- and four-digit HLA alleles of and amino acid polymorphisms encoded by the eight class I and class II HLA genes (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1). We conducted HLA imputation for each data set separately by using HLA and SNP genotypes from the Type 1 Diabetes Genetics Consortium (T1DGC; n = 5,225), which has demonstrated a high imputation accuracy for classical HLA alleles,24,26,31 as a reference panel. We obtained information on HLA-gene polymorphisms from the IMGT/HLA Database.32 Amino acid sequences encoded by the imputed HLA genes are indicated in Figure S1. For HLA amino acid positions, we indicate the start codon of the mature HLA protein as position 1, and we label the codon 5′ to this site as −1.24 SNP2HLA checks concordance of allele strands of the A/T or G/C SNPs between the data set and the reference panel on the basis of allele-frequency comparison.24 We applied postimputation QC criteria of MAF > 0.1% for the association analysis.