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Cell Specific eQTL Analysis without Sorting Cells.

ABSTRACT: The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.

SUBMITTER: Westra HJ 

PROVIDER: S-EPMC4425538 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Cell Specific eQTL Analysis without Sorting Cells.

Westra Harm-Jan HJ   Arends Danny D   Esko Tõnu T   Peters Marjolein J MJ   Schurmann Claudia C   Schramm Katharina K   Kettunen Johannes J   Yaghootkar Hanieh H   Fairfax Benjamin P BP   Andiappan Anand Kumar AK   Li Yang Y   Fu Jingyuan J   Karjalainen Juha J   Platteel Mathieu M   Visschedijk Marijn M   Weersma Rinse K RK   Kasela Silva S   Milani Lili L   Tserel Liina L   Peterson Pärt P   Reinmaa Eva E   Hofman Albert A   Uitterlinden André G AG   Rivadeneira Fernando F   Homuth Georg G   Petersmann Astrid A   Lorbeer Roberto R   Prokisch Holger H   Meitinger Thomas T   Herder Christian C   Roden Michael M   Grallert Harald H   Ripatti Samuli S   Perola Markus M   Wood Andrew R AR   Melzer David D   Ferrucci Luigi L   Singleton Andrew B AB   Hernandez Dena G DG   Knight Julian C JC   Melchiotti Rossella R   Lee Bernett B   Poidinger Michael M   Zolezzi Francesca F   Larbi Anis A   Wang De Yun de Y   van den Berg Leonard H LH   Veldink Jan H JH   Rotzschke Olaf O   Makino Seiko S   Salomaa Veikko V   Strauch Konstantin K   Völker Uwe U   van Meurs Joyce B J JB   Metspalu Andres A   Wijmenga Cisca C   Jansen Ritsert C RC   Franke Lude L  

PLoS genetics 20150508 5

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphoc  ...[more]

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