Fig. 6: Genetic relationships between IgA levels and human disease traits.

a genome-wide genetic correlation analyses between IgA levels and autoimmune, infectious, and cardio-metabolic traits after exclusion of the HLA region (*P < 0.05; two-sided unadjusted P-values for genetic correlation by LD score regression). Supplementary Table 12 provides genetic correlations with and without HLA with P-values for each trait, and references to the original GWAS studies; the error bars correspond to 95% confidence intervals for genetic correlation coefficients. b Meta-PheWAS of genome-wide polygenic score (GPS) for IgA levels across eMERGE-III and UKBB biobanks (total N = 556,656). c Meta-PheWAS of GPS for IgA levels without the HLA region (UKBB and eMERGE-III, total N = 556,656). In (b) and (c), the y-axis shows –log10 (P-value); each triangle represents an individual phenotype (phecode) tested as an outcome against the GPS for IgA levels as a predictor; an upward triangle indicates a positive (risk) association, while a downward triangle indicates a negative (protective) association; two-sided unadjusted P-value corresponds to the fixed effects meta-analysis across the two biobanks based on logistic regression adjusted for age, sex, site, genotyping batch, and principal components of ancestry; the red line corresponds to the Bonferroni-corrected significance threshold for 1523 phecodes tested (alpha = 0.05/1523 = 3.28 × 10⁻⁵); the phenotypes are grouped by organ system (or relevant disease category) and sorted based on their statistical significance within each group. Supplementary Table 13 provides a comparison of significant PheWAS associations with and without the HLA region.