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Title (Primary) Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci
Author Kirsten, H.; Al-Hasani, H.; Holdt, L.; Gross, A.; Beutner, F.; Krohn, K.; Ahnert, P.; Burkhardt, R.; Reiche, K.; Hackermüller, J.; Löffler, M.; Teupser, D.; Thiery, J.; Scholz, M.;
Journal Human Molecular Genetics
Year 2015
Department PROTEOM;
Volume 24
Issue 16
Language englisch;
POF III (all) F11; T42;
Supplements https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/hmg/24/16/10.1093_hmg_ddv194/2/ddv194_Supplementary_Data.zip?Expires=1586345828&Signature=piIqFTKN~n7HkMn3yy8R9a90ve~yB8eeuJTmcfvdhVfuABPu-K3HlYJ1rkMWAHQc5kVvgFTUxGux1IF~zsoo~RllStW7SAynjXE92XWvCs4dUwVTli1XZ8baCa9xGfy5b~82ZJYcBRLXkPpoZhQs3WbTj71ARlZaB3gWELjDdJMz9d~BwgbOab4-Cccx2PIUBxkXMe1iXu4vyzuun1AJmlgiaAhCscML2c8Q8LqjnhkQW0Q-7fdRtaGl4OuAU1WWV1OZdJ-5uqERQrnqeRB~uEOd2qlewt-h9urMKrB009S37T0sLJSL5tqRQyvneKgwfUjd4BqFS4jDAYzCFvNADA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
UFZ wide themes RU3;

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2,112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters, and enrichment of co-localised functional elements.

We found eQTLs for about 85% of analysed genes, 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels, and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs, however, our data suggests that most cis-heritability of these transcripts seems explained. Dissection of co-localised functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes.

In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene-expression, pathways and disease-related processes.

ID 16196
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=16196
Kirsten, H., Al-Hasani, H., Holdt, L., Gross, A., Beutner, F., Krohn, K., Ahnert, P., Burkhardt, R., Reiche, K., Hackermüller, J., Löffler, M., Teupser, D., Thiery, J., Scholz, M. (2015):
Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci
Hum. Mol. Genet. 24 (16), 4746 - 4763