We assessed whether these numbers were significantly higher than expected, by using the same strategy that we had used to assess the enrichment of trait-associated SNPs and the HLA; we ran 100 permutations. We kept per permutation the cis-eQTL list as it was, but generated a permuted set of trans-eQTLs, equal in size to the original set of non-permuted trans-eQTLs. This enabled us to determine per permutation round how many unique pairs of SNPs converge on the same gene(s). We subsequently fitted a generalized extreme value distribution, permitting us to estimate realistic enrichment significance estimates.
