Article abstract

Nature Genetics 39, 1217 - 1224 (2007)
Published online: 16 September 2007 | doi:10.1038/ng2142

Population genomics of human gene expression

Barbara E Stranger1, Alexandra C Nica1, Matthew S Forrest1, Antigone Dimas1, Christine P Bird1, Claude Beazley1, Catherine E Ingle1, Mark Dunning2, Paul Flicek3, Daphne Koller4, Stephen Montgomery1, Simon Tavaré2, Panos Deloukas1 & Emmanouil T Dermitzakis1

Genetic variation influences gene expression, and this variation in gene expression can be efficiently mapped to specific genomic regions and variants. Here we have used gene expression profiling of Epstein-Barr virus–transformed lymphoblastoid cell lines of all 270 individuals genotyped in the HapMap Consortium to elucidate the detailed features of genetic variation underlying gene expression variation. We find that gene expression is heritable and that differentiation between populations is in agreement with earlier small-scale studies. A detailed association analysis of over 2.2 million common SNPs per population (5% frequency in HapMap) with gene expression identified at least 1,348 genes with association signals in cis and at least 180 in trans. Replication in at least one independent population was achieved for 37% of cis signals and 15% of trans signals, respectively. Our results strongly support an abundance of cis-regulatory variation in the human genome. Detection of trans effects is limited but suggests that regulatory variation may be the key primary effect contributing to phenotypic variation in humans. We also explore several methodologies that improve the current state of analysis of gene expression variation.

  1. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  2. Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  3. European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
  4. Computer Science Department, Gates Building 1A, Stanford University, Stanford, California 94305-9010, USA.

Correspondence to: Emmanouil T Dermitzakis1 e-mail:

Correspondence to: Panos Deloukas1 e-mail:


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