A genome-wide association study of global gene expression (original) (raw)
- Article
- Published: 16 September 2007
- Liming Liang3 na1,
- Miriam F Moffatt1 na1,
- Wei Chen3,
- Simon Heath4,
- Kenny C C Wong1,
- Jenny Taylor2,
- Edward Burnett5,
- Ivo Gut4,
- Martin Farrall2,
- G Mark Lathrop4,
- Gonçalo R Abecasis3 &
- …
- William O C Cookson1
Nature Genetics volume 39, pages 1202–1207 (2007)Cite this article
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Abstract
We have created a global map of the effects of polymorphism on gene expression in 400 children from families recruited through a proband with asthma. We genotyped 408,273 SNPs and identified expression quantitative trait loci from measurements of 54,675 transcripts representing 20,599 genes in Epstein-Barr virus–transformed lymphoblastoid cell lines. We found that 15,084 transcripts (28%) representing 6,660 genes had narrow-sense heritabilities (_H_2) > 0.3. We executed genome-wide association scans for these traits and found peak lod scores between 3.68 and 59.1. The most highly heritable traits were markedly enriched in Gene Ontology descriptors for response to unfolded protein (chaperonins and heat shock proteins), regulation of progression through the cell cycle, RNA processing, DNA repair, immune responses and apoptosis. SNPs that regulate expression of these genes are candidates in the study of degenerative diseases, malignancy, infection and inflammation. We have created a downloadable database to facilitate use of our findings in the mapping of complex disease loci.
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Acknowledgements
The study was funded by the Wellcome Trust, the Medical Research Council, the French Ministry of Higher Education and Research and the US National Institutes of Health (the National Human Genome Research Institute and the National Heart, Lung and Blood Institute).
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Author notes
- Anna L Dixon, Liming Liang and Miriam F Moffatt: These authors contributed equally to this work.
Authors and Affiliations
- National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK
Anna L Dixon, Miriam F Moffatt, Kenny C C Wong & William O C Cookson - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
Anna L Dixon, Jenny Taylor & Martin Farrall - Department of Biostatistics, Center for Statistical Genetics, School of public Health, Ann Arbor, 48109-2029, Michigan, USA
Liming Liang, Wei Chen & Gonçalo R Abecasis - Centre National de Génotypage, Institut Génomique, Commissariat à l′Énergie Atomique, Evry, 91057, France
Simon Heath, Ivo Gut & G Mark Lathrop - European Collection of Cell Cultures (ECACC), Porton Down, SP4 0JG, UK
Edward Burnett
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Correspondence toWilliam O C Cookson.
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Dixon, A., Liang, L., Moffatt, M. et al. A genome-wide association study of global gene expression.Nat Genet 39, 1202–1207 (2007). https://doi.org/10.1038/ng2109
- Received: 31 May 2006
- Accepted: 02 July 2007
- Published: 16 September 2007
- Issue Date: October 2007
- DOI: https://doi.org/10.1038/ng2109