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 the common C4 structural haplotypes for each individual. The five most common structural forms of the C4A/C4B locus (BS, AL, AL-BS, AL-BL, and AL-AL) could be inferred with reasonably high accuracy (generally 0.70 < r2 < 1.00). The imputed C4 alleles were tested for association with BD in a joint logistic regression that included (i) terms for dosages of the five most common C4 structural haplotypes (AL-BS, AL-BL, AL-AL, BS, and AL), (ii) rs13195402 genotype (top lead SNP in the MHC) and (iii) PCs as per the GWAS. The genetically regulated expression of C4A was predicted from the imputed C4 alleles using a model previously described63. Predicted C4A expression was tested for association with BD in a joint logistic regression that included (i) predicted C4A expression, (ii) rs13195402 genotype (top lead SNP in the MHC) and (iii) PCs as per the GWAS.
