Article abstract
Nature Genetics 39, 1208 - 1216 (2007)
Published online: 16 September 2007 | doi:10.1038/ng2119
Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes
Harald H H Göring1, Joanne E Curran1, Matthew P Johnson1, Thomas D Dyer1, Jac Charlesworth1, Shelley A Cole1, Jeremy B M Jowett2,3, Lawrence J Abraham4, David L Rainwater1, Anthony G Comuzzie1, Michael C Mahaney1, Laura Almasy1, Jean W MacCluer1, Ahmed H Kissebah5, Gregory R Collier3,6, Eric K Moses1 & John Blangero1,3
Abstract
Quantitative differences in gene expression are thought to contribute to phenotypic differences between individuals. We generated genome-wide transcriptional profiles of lymphocyte samples from 1,240 participants in the San Antonio Family Heart Study. The expression levels of 85% of the 19,648 detected autosomal transcripts were significantly heritable. Linkage analysis uncovered >1,000 cis-regulated transcripts at a false discovery rate of 5% and showed that the expression quantitative trait loci with the most significant linkage evidence are often located at the structural locus of a given transcript. To highlight the usefulness of this much-enlarged map of cis-regulated transcripts for the discovery of genes that influence complex traits in humans, as an example we selected high-density lipoprotein cholesterol concentration as a phenotype of clinical importance, and identified the cis-regulated vanin 1 (VNN1) gene as harboring sequence variants that influence high-density lipoprotein cholesterol concentrations.
- Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA.
- International Diabetes Institute, Caulfield, Victoria 3162, Australia.
- ChemGenex Pharmaceuticals, Geelong, Victoria 3216, Australia.
- School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Western Australia 6009, Australia.
- TOPS Center for Obesity and Metabolic Research, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
- Metabolic Research Unit, School of Health Sciences, Deakin University, Waurn Ponds, Victoria 3216, Australia.
Correspondence to: Harald H H Göring1 e-mail: hgoring@sfbrgenetics.org
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