Mapping the genetic architecture of gene regulation in whole blood.
<h4>Background</h4>We aimed to assess whether whole blood expression quantitative trait loci (eQTLs) with effects in cis and trans are robust and can be used to identify regulatory pathways affecting disease susceptibility.<h4>Materials and methods</h4>We performed whole-geno...
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| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2014
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/8a06b9b27f8b44a090d237a22b4da188 |
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| Sumario: | <h4>Background</h4>We aimed to assess whether whole blood expression quantitative trait loci (eQTLs) with effects in cis and trans are robust and can be used to identify regulatory pathways affecting disease susceptibility.<h4>Materials and methods</h4>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.<h4>Results</h4>In the KORA F4 study, 4,116 cis-eQTLs (defined as SNP-probe pairs where the SNP is located within a 500 kb window around the transcription unit) and 94 trans-eQTLs reached genome-wide significance and overall 91% (92% of cis-, 84% of trans-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.<h4>Conclusions</h4>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. |
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