We observed large and statistically significant enrichments for many functional categories. A few categories stood out in particular. First, regions conserved in mammals [21] showed the largest enrichment of any category, with 2.6% of SNPs explaining an estimated 35% of SNP-heritability on average across traits (P < 10−6 for enrichment). This is a significantly higher average enrichment than for coding regions, and provides evidence for the biological importance of conserved regions, despite the fact that the biochemical function of many conserved regions remains uncharacterized [37]. Second, FANTOM5 Enhancers [23] were extremely enriched in the three immunological diseases, with 0.4% of SNPs explaining an estimated 15% of SNP-heritability on average across these three diseases (P = 10−4, 2×10−4, and 0.03 for Crohn’s disease, Ulcerative Colitis, and Rheumatoid arthritis, respectively), but showed no evidence of enrichment for non-immunological traits (Figure 5). The immune-specific enrichment could be because immune cells have better coverage, altered degradation, and/or a higher number of enhancers. We did not see a large enrichment of super-enhancers vs. regular enhancers; the estimates for enrichment were 1.8x (s.e. 0.2) for super-enhancers
