Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes

Nat Genet. 2007 Oct;39(10):1208-16. doi: 10.1038/ng2119. Epub 2007 Sep 16.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amidohydrolases / genetics
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / genetics
  • Cell Adhesion Molecules / genetics
  • Cholesterol, HDL / genetics
  • Cholesterol, HDL / metabolism
  • GPI-Linked Proteins
  • Gene Expression Profiling
  • Genetic Linkage
  • Genetic Markers
  • Genotype
  • Humans
  • Lymphocytes / metabolism
  • Mexican Americans / genetics
  • Phenotype*
  • Promoter Regions, Genetic
  • Quantitative Trait Loci*
  • Transcription, Genetic*


  • Cell Adhesion Molecules
  • Cholesterol, HDL
  • GPI-Linked Proteins
  • Genetic Markers
  • Amidohydrolases
  • pantetheinase