A genome-wide association study of global gene expression.
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.
Dixon
Anna L
AL
National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
Liang
Liming
L
Moffatt
Miriam F
MF
Chen
Wei
W
Heath
Simon
S
Wong
Kenny C C
KC
Taylor
Jenny
J
Burnett
Edward
E
Gut
Ivo
I
Farrall
Martin
M
Lathrop
G Mark
GM
Abecasis
Gonçalo R
GR
Cookson
William O C
WO
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
D006360:Heat-Shock Proteins; D018833:Chaperonins