title: Population genomics of human gene expression.
abstract: 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.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Stranger
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Nica
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Forrest
authors.forename: Antigone
authors.initials: A
authors.lastname: Dimas
authors.forename: Christine P
authors.initials: CP
authors.lastname: Bird
authors.forename: Claude
authors.initials: C
authors.lastname: Beazley
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Ingle
authors.forename: Mark
authors.initials: M
authors.lastname: Dunning
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
authors.forename: Stephen
authors.initials: S
authors.lastname: Montgomery
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
mesh_terms: D000483:Alleles; D045744:Cell Line, Tumor; D002889:Chromosomes, Human, Pair 2; D015870:Gene Expression; D020869:Gene Expression Profiling; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics; D024363:Transcription Initiation Site
chemical_list: D012097:Repressor Proteins; C500760:SPRED2 protein, human