title: A systematic eQTL study of cis-trans epistasis in 210 HapMap individuals.
abstract: 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 × 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 × 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.
authors.affiliation: Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.forename: Jens R
authors.initials: JR
authors.lastname: Wendland
authors.forename: Britta
authors.initials: B
authors.lastname: Haenisch
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D030561:Databases, Nucleic Acid; D004843:Epistasis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D055106:Genome-Wide Association Study; D060148:HapMap Project; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D059467:Transcriptome
chemical_list: D005819:Genetic Markers