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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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).

Author information

Author notes

    • Anna L Dixon
    • , Liming Liang
    •  & Miriam F Moffatt

    These authors contributed equally to this work.


  1. National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.

    • Anna L Dixon
    • , Miriam F Moffatt
    • , Kenny C C Wong
    •  & William O C Cookson
  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

    • Anna L Dixon
    • , Jenny Taylor
    •  & Martin Farrall
  3. Center for Statistical Genetics, Department of Biostatistics, School of public Health, Ann Arbor, Michigan 48109-2029, USA.

    • Liming Liang
    • , Wei Chen
    •  & Gonçalo R Abecasis
  4. Centre National de Génotypage, Institut Génomique, Commissariat à l′Énergie Atomique, 91057 Evry, France.

    • Simon Heath
    • , Ivo Gut
    •  & G Mark Lathrop
  5. European Collection of Cell Cultures (ECACC), Porton Down, SP4 0JG, UK.

    • Edward Burnett


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Corresponding author

Correspondence to William O C Cookson.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–2

Excel files

  1. 1.

    Supplementary Table 1

    Transcripts and SNPs with H2>0.3 and LOD scores for association>6.

  2. 2.

    Supplementary Table 2

    Summary of sequential search for independent associations of SNPs with individual transcripts

  3. 3.

    Supplementary Table 3

    Potential Master Regulators

  4. 4.

    Supplementary Table 4

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

  5. 5.

    Supplementary Table 5

    Lists of genes in the three most significant GO-BP classes

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