A systematic eQTL study of cis-trans epistasis in 210 HapMap individuals

We aimed at identifying transcripts whose expression is regulated by a SNP-SNP interaction. Out of 47 294 expression phenotypes we used 3107 transcripts that survived an extensive quality control and 86 613 linkage disequilibrium-pruned SNP markers that have been genotyped in 210 individuals. For each transcript we defined cis-SNPs, tested them for epistasis with all trans-SNPs, and corrected all observed cis-trans-regulated expression effects for multiple testing. We determined that the expression of about 15% of all included transcripts is regulated by a significant two-locus interaction, which is more than expected (P=2.86 x 10(-144)). Our findings suggest further that cis-markers with so called 'marginal effects' are more likely to be involved in two-locus gene regulation than expected (P=8.27 x 10(-05)), although the majority of interacting cis-markers showed no one-locus regulation. Furthermore, we found evidence that gene-mediated trans-effects are not a major source of epistasis, as no enrichment of genes has been found in close vicinity of trans-SNPs. In addition, our data support the notion that neither chromosomal regions nor cellular processes are enriched in epistatic interactions. Finally, some of the cis-trans regulated genes have been found in genome-wide association studies, which might be interesting for follow-up studies of the corresponding disorders. In summary, our results provide novel insights into the complex genome-transcriptome regulation. European Journal of Human Genetics (2012) 20, 97-101; doi:10.1038/ejhg.2011.156; published online 17 August 2011