Mapping the Genetic Architecture of Gene Regulation in Whole Blood Katharina Schramm Carola Marzi Claudia Schurmann Maren Carstensen Eva Reinmaa Reiner Biffar Gertrud Eckstein Christian Gieger Hans-Jörgen Grabe Georg Homuth Gabriele Kastenmüller Reedik Mägi Andres Metspalu Evelin Mihailov Annette Peters Astrid Petersmann Michael Roden Konstantin Strauch Karsten Suhre Alexander Teumer Uwe Völker Henry Völzke Rui Wang-Sattler Melanie Waldenberger Thomas Meitinger Thomas Illig Christian Herder Harald Grallert Holger Prokisch 10.1371/journal.pone.0093844 https://plos.figshare.com/articles/dataset/_Mapping_the_Genetic_Architecture_of_Gene_Regulation_in_Whole_Blood_/1001075 <div><p>Background</p><p>We aimed to assess whether whole blood expression quantitative trait loci (eQTLs) with effects in <i>cis</i> and <i>trans</i> are robust and can be used to identify regulatory pathways affecting disease susceptibility.</p><p>Materials and Methods</p><p>We performed whole-genome eQTL analyses in 890 participants of the KORA F4 study and in two independent replication samples (SHIP-TREND, N = 976 and EGCUT, N = 842) using linear regression models and Bonferroni correction.</p><p>Results</p><p>In the KORA F4 study, 4,116 <i>cis</i>-eQTLs (defined as SNP-probe pairs where the SNP is located within a 500 kb window around the transcription unit) and 94 <i>trans</i>-eQTLs reached genome-wide significance and overall 91% (92% of <i>cis-</i>, 84% of <i>trans-</i>eQTLs) were confirmed in at least one of the two replication studies. Different study designs including distinct laboratory reagents (PAXgene™ vs. Tempus™ tubes) did not affect reproducibility (separate overall replication overlap: 78% and 82%). Immune response pathways were enriched in cis- and trans-eQTLs and significant cis-eQTLs were partly coexistent in other tissues (cross-tissue similarity 40–70%). Furthermore, four chromosomal regions displayed simultaneous impact on multiple gene expression levels in trans, and 746 eQTL-SNPs have been previously reported to have clinical relevance. We demonstrated cross-associations between eQTL-SNPs, gene expression levels in trans, and clinical phenotypes as well as a link between eQTLs and human metabolic traits via modification of gene regulation in cis.</p><p>Conclusions</p><p>Our data suggest that whole blood is a robust tissue for eQTL analysis and may be used both for biomarker studies and to enhance our understanding of molecular mechanisms underlying gene-disease associations.</p></div> 2014-04-16 02:59:15 Computational biology genome analysis Genome-wide association studies genetics Heredity Quantitative traits Human genetics Genetic association studies gene expression Network Analysis Regulatory networks Diagnostic medicine hematology Pathology and laboratory medicine molecular pathology