Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

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    Author
    Law, PJ; Berndt, SI; Speedy, HE; Camp, NJ; Sava, GP; Skibola, CF; Holroyd, A; Joseph, V; Sunter, NJ; Nieters, A; ...
    Date
    2017-02-06
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Southey, Melissa; Milne, Roger; Giles, Graham
    Affiliation
    Melbourne School of Population and Global Health
    Clinical Pathology
    Metadata
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    Document Type
    Journal Article
    Citations
    Law, P. J., Berndt, S. I., Speedy, H. E., Camp, N. J., Sava, G. P., Skibola, C. F., Holroyd, A., Joseph, V., Sunter, N. J., Nieters, A., Bea, S., Monnereau, A., Martin-Garcia, D., Goldin, L. R., Clot, G., Teras, L. R., Quintela, I., Birmann, B. M., Jayne, S. ,... Slager, S. L. (2017). Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/ncomms14175.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257916
    DOI
    10.1038/ncomms14175
    Abstract
    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

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