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Originally published in Science Express on 30 July 2009
Science 4 September 2009:
Vol. 325. no. 5945, pp. 1246 - 1250
DOI: 10.1126/science.1174148
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Reports

Common Regulatory Variation Impacts Gene Expression in a Cell Type–Dependent Manner

Antigone S. Dimas,1,* Samuel Deutsch,2,* Barbara E. Stranger,1,3,* Stephen B. Montgomery,1,* Christelle Borel,2 Homa Attar-Cohen,2 Catherine Ingle,1 Claude Beazley,1 Maria Gutierrez Arcelus,1 Magdalena Sekowska,1 Marilyne Gagnebin,2 James Nisbett,1 Panos Deloukas,1 Emmanouil T. Dermitzakis,1,{dagger},{ddagger} Stylianos E. Antonarakis2,{ddagger}

Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type–specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type–specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type–specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.

1 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1HH, Cambridge, UK.
2 Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, CH-1211, Switzerland.
3 Division of Genetics, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, 02115 USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, CH-1211, Switzerland.

{ddagger} To whom correspondence should be addressed. E-mail: emmanouil.dermitzakis{at}unige.ch (E.T.D.); stylianos.antonarakis{at}unige.ch (S.E.A.)

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing.
G. A. Heap, J. H.M. Yang, K. Downes, B. C. Healy, K. A. Hunt, N. Bockett, L. Franke, P. C. Dubois, C. A. Mein, R. J. Dobson, et al. (2010)
Hum. Mol. Genet. 19, 122-134
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