Extended Data Fig. 3: Association tests within the MHC to HIV-1 viral load.

The x-axis shows the genomic positions of chromosome 6 (build 37), and the y-axis is the -log₁₀ (P-value) obtained from two-sided regression analyses for SNPs (gray), classical HLA alleles (blue) and amino acids (red). The dashed black line indicates the genome-wide significance threshold (P = 5 × 10⁻⁸). For biallelic markers, results were calculated by a linear regression model including sex, cohort-specific principal components and ancestry indicator as covariates (circle). Association at amino acid positions with more than two residues was calculated using a multi-degree-of-freedom omnibus test (one-sided F-test) including the same covariates (diamond). The top associated amino acid, classical HLA allele and SNPs are annotated in the figure. a, Of all variants tested, the top hit maps to amino acid position 97 in HLA-B. b, Subsequent conditional analysis controlling for all residues at position 97 in HLA-B revealed an independent association at position 67 in HLA-B. c, Results conditioned on position 97 and 67 in HLA-B showed a third signal at position 156 in HLA-B. d, Results conditioned on position 97, 67 and 156 in HLA-B showed position 77 in HLA-A has the strongest association signal outside HLA-B among all amino acid positions. e, Results conditioned on all amino acid positions in HLA-B. Notably, amino acid positions were more significant than any single SNP or classical HLA allele in each conditional analysis for the three amino acid positions in HLA-B.