Cell Specific eQTL Analysis without Sorting Cells

Harm-Jan Westra*, Danny Arends, Tonu Esko, Marjolein J. Peters, Claudia Schurmann, Katharina Schramm, Johannes Kettunen, Hanieh Yaghootkar, Benjamin P. Fairfax, Anand Kumar Andiappan, Yang Li, Jingyuan Fu, Juha Karjalainen, Mathieu Platteel, Marijn Visschedijk, Rinse K. Weersma, Silva Kasela, Lili Milani, Liina Tserel, Part PetersonEva Reinmaa, Albert Hofman, Andre G. Uitterlinden, Fernando Rivadeneira, Georg Homuth, Astrid Petersmann, Roberto Lorbeer, Holger Prokisch, Thomas Meitinger, Christian Herder, Michael Roden, Harald Grallert, Samuli Ripatti, Markus Perola, Andrew R. Wood, David Melzer, Luigi Ferrucci, Andrew B. Singleton, Dena G. Hernandez, Julian C. Knight, Rossella Melchiotti, Bernett Lee, Michael Poidinger, Francesca Zolezzi, Anis Larbi, De Yun Wang, Leonard H. van den Berg, Jan H. Veldink, Olaf Rotzschke, Seiko Makino, Veikko Salomaa, Konstantin Strauch, Uwe Voelker, Joyce B. J. van Meurs, Andres Metspalu, Cisca Wijmenga, Ritsert C. Jansen, Lude Franke

*Corresponding author for this work

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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.

Original languageEnglish
Article number1005223
Number of pages17
JournalPLoS genetics
Volume11
Issue number5
DOIs
Publication statusPublished - May-2015

Keywords

  • ACTIVE CROHNS-DISEASE
  • GENE-EXPRESSION
  • WIDE ASSOCIATION
  • DNA METHYLATION
  • VARIANTS
  • HETEROGENEITY
  • BLOOD

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