10.1371/journal.pone.0093844
Katharina Schramm
Katharina
Schramm
Carola Marzi
Carola
Marzi
Claudia Schurmann
Claudia
Schurmann
Maren Carstensen
Maren
Carstensen
Eva Reinmaa
Eva
Reinmaa
Reiner Biffar
Reiner
Biffar
Gertrud Eckstein
Gertrud
Eckstein
Christian Gieger
Christian
Gieger
Hans-Jörgen Grabe
Hans-Jörgen
Grabe
Georg Homuth
Georg
Homuth
Gabriele Kastenmüller
Gabriele
Kastenmüller
Reedik Mägi
Reedik
Mägi
Andres Metspalu
Andres
Metspalu
Evelin Mihailov
Evelin
Mihailov
Annette Peters
Annette
Peters
Astrid Petersmann
Astrid
Petersmann
Michael Roden
Michael
Roden
Konstantin Strauch
Konstantin
Strauch
Karsten Suhre
Karsten
Suhre
Alexander Teumer
Alexander
Teumer
Uwe Völker
Uwe
Völker
Henry Völzke
Henry
Völzke
Rui Wang-Sattler
Rui
Wang-Sattler
Melanie Waldenberger
Melanie
Waldenberger
Thomas Meitinger
Thomas
Meitinger
Thomas Illig
Thomas
Illig
Christian Herder
Christian
Herder
Harald Grallert
Harald
Grallert
Holger Prokisch
Holger
Prokisch
Mapping the Genetic Architecture of Gene Regulation in Whole Blood
Public Library of Science
2014
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
2014-04-16 02:59:15
Dataset
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>