To investigate the major histocompatibility complex (MHC; chr6:24–34 Mb on hg19), the alleles of complement component 4 genes (C4A and C4B) were imputed in 47 PGC cohorts for which individual-level genotype data were accessible, totaling 32,749 BD cases and 53,370 controls. The imputation reference panel comprised 2,530 reference haplotypes of MHC SNPs and C4 alleles, generated using a sample of 1,265 individuals with whole-genome sequence data, from the Genomic Psychiatry cohort114. Briefly, imputation of C4 as a multi-allelic variant was performed using Beagle v4.1115,116, using SNPs from the MHC region that were also in the haplotype reference panel. Within the Beagle pipeline, the reference panel was first converted to bref format. We used the conform-gt tool to perform strand-flipping and filtering of specific SNPs for which strand remained ambiguous. Beagle was run using default parameters with two key exceptions: we used the GRCh37 PLINK recombination map, and we set the output to include genotype probability (i.e., GP field in VCF) for correct downstream probabilistic estimation of C4A and C4B joint dosages. The output consisted of dosage estimates for each of
