At the 0.001 threshold, the majority of trans associations are caused by SNPs from the first category, i.e. those with cis-regulatory effects, showing 3- to 6-fold enrichment relative to the total SNPs tested (Fisher's exact test p-values 10−10-10−24, depending on the population except the YRI population, where it is not significant). Some SNPs were significantly associated with expression of multiple genes (up to 6 genes for a single SNP). The numbers of SNPs that are associated with more than 1 gene are: CEU = 29 SNPs, CHB = 13, JPT = 7, YRI = 4. A total of 8 genes had a trans association on the same chromosome (distance > 1 Mb) with distances ranging from 1003413 bps (potential cis effect) to 187659746 bps. If gene expression perturbations are similar in underlying genetic effects as whole organism perturbations and disease, then this last result suggests that the majority of the common phenotypic variation in humans is driven by variants in regulatory elements, rather than variants in protein-coding sequences, providing some potential answers to the long standing question of the relative contribution of regulatory and coding causal variants to complex phenotypes.
