Genetic correlations reveal the shared genetic architecture of transcription in human peripheral blood

Lukowski, Samuel W., Lloyd-Jones, Luke R., Holloway, Alexander, Kirsten, Holger, Hemani, Gibran, Yang, Jian, Small, Kerrin, Zhao, Jing, Metspalu, Andres, Dermitzakis, Emmanouil T., Gibson, Greg, Spector, Timothy D., Thiery, Joachim, Scholz, Markus, Montgomery, Grant W., Esko, Tonu, Visscher, Peter M. and Powell, Joseph E. (2017) Genetic correlations reveal the shared genetic architecture of transcription in human peripheral blood. Nature Communications, 8 483: . doi:10.1038/s41467-017-00473-z


Author Lukowski, Samuel W.
Lloyd-Jones, Luke R.
Holloway, Alexander
Kirsten, Holger
Hemani, Gibran
Yang, Jian
Small, Kerrin
Zhao, Jing
Metspalu, Andres
Dermitzakis, Emmanouil T.
Gibson, Greg
Spector, Timothy D.
Thiery, Joachim
Scholz, Markus
Montgomery, Grant W.
Esko, Tonu
Visscher, Peter M.
Powell, Joseph E.
Title Genetic correlations reveal the shared genetic architecture of transcription in human peripheral blood
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-09-07
Year available 2017
Sub-type Article (original research)
DOI 10.1038/s41467-017-00473-z
Open Access Status DOI
Volume 8
Issue 483
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Transcript co-expression is regulated by a combination of shared genetic and environmental factors. Here, we estimate the proportion of co-expression that is due to shared genetic variance. To do so, we estimated the genetic correlations between each pairwise combination of 2469 transcripts that are highly heritable and expressed in whole blood in 1748 unrelated individuals of European ancestry. We identify 556 pairs with a significant genetic correlation of which 77% are located on different chromosomes, and report 934 expression quantitative trait loci, identified in an independent cohort, with significant effects on both transcripts in a genetically correlated pair. We show significant enrichment for transcription factor control and physical proximity through chromatin interactions as possible mechanisms of shared genetic control. Finally, we construct networks of interconnected transcripts and identify their underlying biological functions. Using genetic correlations to investigate transcriptional co-regulation provides valuable insight into the nature of the underlying genetic architecture of gene regulation.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Centre for Neurogenetics and Statistical Genomics Publications
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 06 Oct 2017, 15:53:03 EST by Kirstie Asmussen on behalf of Institute for Molecular Bioscience