Systematic identification of trans eQTLs as putative drivers of known disease associations

Westra, Harm-Jan, Peters, Marjolein J., Esko, Tonu, Yaghootkar, Hanieh, Schurmann, Claudia, Kettunen, Johannes, Christiansen, Mark W., Fairfax, Benjamin P., Schramm, Katharina, Powell, Joseph E., Zhernakova, Alexandra, Zhernakova, Daria V., Veldink, Jan H., Van den Berg, Leonard H., Karjalainen, Juha, Withoff, Sebo, Uitterlinden, Andre G., Hofman, Albert, Rivadeneira, Fernando, Hoen, Peter A. C't, Reinmaa, Eva, Fischer, Krista, Nelis, Mari, Milani, Lili, Melzer, David, Ferrucci, Luigi, Singleton, Andrew B., Hernandez, Dena G., Nalls, Michael A., Homuth, Georg, Nauck, Matthias, Radke, Doerte, Voelker, Uwe, Perola, Markus, Salomaa, Veikko, Brody, Jennifer, Suchy-Dicey, Astrid, Gharib, Sina A., Enquobahrie, Daniel A., Lumley, Thomas, Montgomery, Grant W., Makino, Seiko, Prokisch, Holger, Herder, Christian, Roden, Michael, Grallert, Harald, Meitinger, Thomas, Strauch, Konstantin, Li, Yang, Jansen, Ritsert C., Visscher, Peter M., Knight, Julian C., Psaty, Bruce M., Ripatti, Samuli, Teumer, Alexander, Frayling, Timothy M., Metspalu, Andres, van Meurs, Joyce B. J. and Franke, Lude (2013) Systematic identification of trans eQTLs as putative drivers of known disease associations. Nature Genetics, 45 10: 1238-U195. doi:10.1038/ng.2756

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Author Westra, Harm-Jan
Peters, Marjolein J.
Esko, Tonu
Yaghootkar, Hanieh
Schurmann, Claudia
Kettunen, Johannes
Christiansen, Mark W.
Fairfax, Benjamin P.
Schramm, Katharina
Powell, Joseph E.
Zhernakova, Alexandra
Zhernakova, Daria V.
Veldink, Jan H.
Van den Berg, Leonard H.
Karjalainen, Juha
Withoff, Sebo
Uitterlinden, Andre G.
Hofman, Albert
Rivadeneira, Fernando
Hoen, Peter A. C't
Reinmaa, Eva
Fischer, Krista
Nelis, Mari
Milani, Lili
Melzer, David
Ferrucci, Luigi
Singleton, Andrew B.
Hernandez, Dena G.
Nalls, Michael A.
Homuth, Georg
Nauck, Matthias
Radke, Doerte
Voelker, Uwe
Perola, Markus
Salomaa, Veikko
Brody, Jennifer
Suchy-Dicey, Astrid
Gharib, Sina A.
Enquobahrie, Daniel A.
Lumley, Thomas
Montgomery, Grant W.
Makino, Seiko
Prokisch, Holger
Herder, Christian
Roden, Michael
Grallert, Harald
Meitinger, Thomas
Strauch, Konstantin
Li, Yang
Jansen, Ritsert C.
Visscher, Peter M.
Knight, Julian C.
Psaty, Bruce M.
Ripatti, Samuli
Teumer, Alexander
Frayling, Timothy M.
Metspalu, Andres
van Meurs, Joyce B. J.
Franke, Lude
Title Systematic identification of trans eQTLs as putative drivers of known disease associations
Formatted title
Systematic identification of trans eQTLs as putative drivers of known disease associations
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2013-10-01
Sub-type Article (original research)
DOI 10.1038/ng.2756
Open Access Status File (Author Post-print)
Volume 45
Issue 10
Start page 1238
End page U195
Total pages 8
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Formatted abstract
Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified and replicated trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously associated with complex traits at genome-wide significance. Some of these SNPs affect multiple genes in trans that are known to be altered in individuals with disease: rs4917014, previously associated with systemic lupus erythematosus (SLE), altered gene expression of C1QB and five type I interferon response genes, both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly alters the 3′ UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal gene. Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 333 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 362 times in Scopus Article | Citations
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Created: Wed, 06 Nov 2013, 01:53:42 EST by Anthony Yeates on behalf of Queensland Brain Institute