Fig. 5: Evolution of the inflammatory disease-associated enhancers.

a Binary map of genes (in black) shared among ≥ 30% of the major chronic inflammatory and autoimmune diseases, illustrating overlap between conditions. b Left: enrichment of Alus in IDEs relative to non-IDEs tested with a hypergeometric enrichment test and Benjamini–Hochberg correction (P < 0.1). Right: proportion of enhancers carrying NF-κB-MA0105.4 motifs; all (left) or great-ape-specific (right). c Proportion of IDEs and non-IDEs containing SNPs associated with chronic inflammatory and autoimmune disorders (P ~ 0). d Left: proportion of enhancers with PS-SNPs. Right: proportion of PS-SNPs within Alus relative to all PS-SNPs in enhancers in IDE versus non-IDE groups. Exact values: P ~ 0 (left), P = 2.03e-07 (right). b (right), c, d Statistical comparisons were performed using pairwise two-sided χ² tests. *** P < 0.001. e Genome browser view of a fragment of positively selected IDE (from the intermediate group) carrying PS-SNP rs6011058-T (selection value P < 2e−5) within an AluYk2 element. Shown are genes linked to the enhancer via the ABC algorithm. Global selection patterns are visualized with the Geography of Genetic Variants Browser. f KLF motifs overlapping rs6011058-T and binding affinity changes of the derived versus ancestral allele, estimated with TFBStools. g PheWas plot was generated using Open Targets Genetics (https://atlas.ctglab.nl/PheWAS) for traits significantly associated with rs6011058-T in FinnGen, UK Biobank, and GWAS Catalog. P-values are derived from GWAS regression models; the horizontal red line marks the Bonferroni significance threshold (P < 1e−5). Source data are provided as a Source Data file.