GWA studies have identified many loci, but it is still often unclear what the affected gene in each locus is. Here we showed that 39% of trait-associated SNPs affect gene expression in cis which is helpful in pinpointing the most likely gene per susceptibility locus. However, GWAS do not immediately provide insight in the trans-effects of these susceptibility variants on downstream genes. Here we identified for 2.6% of all trait-associated SNPs trans-eQTL effects on in total 113 unique genes. While some of these trans-eQTLs are known to be involved in these phenotypes (such as HBG2 in hemoglobin protein levels and ß-Thallasemia), most of these genes have not been implicated before in these complex traits, and provide additional insight in the downstream mechanisms of these variants. Interestingly, 48% of trans-acting trait-associated SNPs map within the HLA, indicating the HLA has a prominent role in regulating peripheral blood gene expression. This might partly explain why the HLA has been found to be associated with so many different diseases.
