Fig. 3: Stepwise regression of the HLA association identifies the major genetic determinants of autoimmune Addison’s disease. | Nature Communications

Fig. 3: Stepwise regression of the HLA association identifies the major genetic determinants of autoimmune Addison’s disease.

From: GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility

Fig. 3

The figure displays the results from the first six steps of regression modeling of the HLA risk effects—alleles and amino acids. Starting with a baseline model comprising sex and five principal components as covariates, we tested every allele and amino acid in turn for association with AAD (Supplementary Note). Additive, recessive, dominant, overdominant, and general variable encodings were compared with likelihood ratio tests and/or Bayesian information criterion. The allele or amino acid residue with most compelling evidence for association was included in the model at every step, and reconsidered at all subsequent steps. Downstream regression models were conditioned on the effects selected from previous models. The y-axes show the –log10 P values from stepwise logistic regressions of 1223 cases and 4097 controls. The dashed horizontal lines indicate genome-wide significance (P < 5 × 10−8). Diamonds mark the most significant effect. Blue color indicates strong linkage disequilibrium (r2) with the most significant effect, gray color indicates no correlation.

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