title: A genome-wide association study of global gene expression.
abstract: We have created a global map of the effects of polymorphism on gene expression in 400 children from families recruited through a proband with asthma. We genotyped 408,273 SNPs and identified expression quantitative trait loci from measurements of 54,675 transcripts representing 20,599 genes in Epstein-Barr virus-transformed lymphoblastoid cell lines. We found that 15,084 transcripts (28%) representing 6,660 genes had narrow-sense heritabilities (H2) > 0.3. We executed genome-wide association scans for these traits and found peak lod scores between 3.68 and 59.1. The most highly heritable traits were markedly enriched in Gene Ontology descriptors for response to unfolded protein (chaperonins and heat shock proteins), regulation of progression through the cell cycle, RNA processing, DNA repair, immune responses and apoptosis. SNPs that regulate expression of these genes are candidates in the study of degenerative diseases, malignancy, infection and inflammation. We have created a downloadable database to facilitate use of our findings in the mapping of complex disease loci.
authors.affiliation: National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Dixon
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Kenny C C
authors.initials: KC
authors.lastname: Wong
authors.forename: Jenny
authors.initials: J
authors.lastname: Taylor
authors.forename: Edward
authors.initials: E
authors.lastname: Burnett
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: William O C
authors.initials: WO
authors.lastname: Cookson
mesh_terms: D018833:Chaperonins / Q000235:genetics; D002648:Child; D005190:Family; D015870:Gene Expression; D015894:Genome, Human; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
chemical_list: D006360:Heat-Shock Proteins; D018833:Chaperonins