Cis-acting variants altering gene expression are a source of phenotypic differences. The cis-acting components of expression variation can be identified through the mapping of differences in allelic expression (AE), which is the measure of relative expression between two allelic transcripts. We generated a map of AE associated SNPs using quantitative measurements of AE on Illumina Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of European descent, we identified common cis variants affecting 30% (2935/9751) of the measured RefSeq transcripts at 0.001 permutation significance. The pervasive influence of cis-regulatory variants, which explain 50% of population variation in AE, extend to full-length transcripts and their isoforms as well as to unannotated transcripts. These strong effects facilitate fine mapping of cis-regulatory SNPs, as demonstrated by dissection of heritable control of transcripts in the systemic lupus erythematosus–associated C8orf13-BLK region in chromosome 8. The dense collection of associations will facilitate large-scale isolation of cis-regulatory SNPs.

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This work was supported by Genome Canada, Genome Québec and Illumina, Inc. T.P. holds a Canada Research Chair. H.H.H.G. carried out work in facilities constructed with support from Research Facilities Improvement Program Grant Number C06 RR017515 from the National Center for Research Resources, National Institutes of Health and a gift from the SBC Foundation.

Author information


  1. McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada.

    • Bing Ge
    • , Tony Kwan
    • , Elin Grundberg
    • , Lisanne Morcos
    • , Dominique J Verlaan
    • , Vonda Koka
    • , Kevin C L Lam
    • , Joana Dias
    • , Alexandre Montpetit
    • , Marie-Michele Joly
    • , Ken Dewar
    • , Eef Harmsen
    • , Jacek Majewski
    •  & Tomi Pastinen
  2. Illumina Inc., San Diego, California, USA.

    • Dmitry K Pokholok
    • , Jennie Le
    •  & Kevin L Gunderson
  3. Department of Human Genetics, McGill University Health Centre, McGill University, Montréal, Québec, Canada.

    • Elin Grundberg
    • , Lisanne Morcos
    • , Dominique J Verlaan
    • , Ken Dewar
    • , Jacek Majewski
    •  & Tomi Pastinen
  4. Department of Medical Genetics, McGill University Health Centre, McGill University, Montréal, Québec, Canada.

    • Elin Grundberg
    • , Lisanne Morcos
    • , Dominique J Verlaan
    • , Ken Dewar
    • , Jacek Majewski
    • , Anna K Naumova
    •  & Tomi Pastinen
  5. Hôpital Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.

    • Vincent Gagné
    • , Daniel Sinnett
    • , Patrick Beaulieu
    • , Robert Hamon
    • , Alexandru Graziani
    •  & Mathieu Blanchette
  6. School of Computer Science, McGill University, Montréal, Québec, Canada.

    • Rose Hoberman
  7. Division of Orthopaedic Surgery, McGill University Health Centre, McGill University, Montréal, Québec, Canada.

    • Edward J Harvey
  8. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.

    • Harald H H Göring
  9. Department of Obstetrics and Gynecology, McGill University, the Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.

    • Anna K Naumova


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T.P. and K.L.G. conceived the research. B.G., D.K.P., T.K., E.G., D.J.V., J.L., K.L.G., D.S. and T.P. designed the experiments. D.K.P., E.G., D.J.V., V.K., K.C.L.L., V.G., J.D. and M.-M.J. conducted the experiments. B.G., D.K.P., H.H.H.G., R. Hoberman, P.B., R. Hamon, A.G., M.B. and T.P. designed the computational and analytical methods. B.G., T.K., L.M., D.J.V., R. Hoberman, A.K.N., K.L.G. and T.P. analyzed the data. E.J.H. contributed primary osteoblast cell lines. T.P. drafted the manuscript and all authors contributed to the final manuscript writing and its revisions.

Competing interests

The authors KL Gunderson, DK Pokholok and J Le are employed by Illumina Inc and KL Gunderson owns stock in the company.

Corresponding author

Correspondence to Tomi Pastinen.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–13, Supplementary Tables 2–5, 7–9 and Supplementary Note

Excel files

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    Supplementary Table 1

    Details of 7785 AE associations detected at permutation significance 0.005

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    Supplementary Table 6

    High confidence full transcript AE associations

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