Population genomics of human gene expression.
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.
Stranger
Barbara E
BE
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Nica
Alexandra C
AC
Forrest
Matthew S
MS
Dimas
Antigone
A
Bird
Christine P
CP
Beazley
Claude
C
Ingle
Catherine E
CE
Dunning
Mark
M
Flicek
Paul
P
Koller
Daphne
D
Montgomery
Stephen
S
Tavaré
Simon
S
Deloukas
Panos
P
Dermitzakis
Emmanouil T
ET
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
D012097:Repressor Proteins; C500760:SPRED2 protein, human