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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.

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Figure 1: Summaries of heritability and association analysis for all genes.
Figure 2: Proportion of significantly associated SNPs and expression trait heritability.
Figure 3: Associations in cis and trans.
Figure 4: Regulators of genes involved in the cell cycle or immune response.

Accession codes


Gene Expression Omnibus


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The study was funded by the Wellcome Trust, the Medical Research Council, the French Ministry of Higher Education and Research and the US National Institutes of Health (the National Human Genome Research Institute and the National Heart, Lung and Blood Institute).

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Corresponding author

Correspondence to William O C Cookson.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–2 (PDF 149 kb)

Supplementary Table 1

Transcripts and SNPs with H2>0.3 and LOD scores for association>6. (XLS 2671 kb)

Supplementary Table 2

Summary of sequential search for independent associations of SNPs with individual transcripts (XLS 55 kb)

Supplementary Table 3

Potential Master Regulators (XLS 456 kb)

Supplementary Table 4

Gene Ontology (Biological Process) analyses for most highly heritable traits (XLS 60 kb)

Supplementary Table 5

Lists of genes in the three most significant GO-BP classes (XLS 1059 kb)

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Dixon, A., Liang, L., Moffatt, M. et al. A genome-wide association study of global gene expression. Nat Genet 39, 1202–1207 (2007).

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