SNPs are included in the null-distribution, as it is known that trait-associated SNPs in general already have different functional properties than randomly selected SNPs58 (e.g. trait-associated SNPs typically map in closer proximity to genes than random SNPs). We also ensured that none of the SNPs in the null-distribution were affecting genes in trans, or were linked to those SNPs (r2 < 0.2 in 1000 genomes). We then identified perfect proxies (r2 = 1.0 in 1000 genomes). For SNPInfo and SNPNexus, we calculated the enrichment for each functional category using a Fisher's exact test. We determined the enhancer enrichment in nine different cell-types using HaploReg, where we averaged the enhancer enrichment over the ten permutations.
