Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

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    Author
    Berndt, SI; Camp, NJ; Skibola, CF; Vijai, J; Wang, Z; Gu, J; Nieters, A; Kelly, RS; Smedby, KE; Monnereau, A; ...
    Date
    2016-03-01
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Southey, Melissa; Giles, Graham; Milne, Roger
    Affiliation
    Melbourne School of Population and Global Health
    Clinical Pathology
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    Document Type
    Journal Article
    Citations
    Berndt, S. I., Camp, N. J., Skibola, C. F., Vijai, J., Wang, Z., Gu, J., Nieters, A., Kelly, R. S., Smedby, K. E., Monnereau, A., Cozen, W., Cox, A., Wang, S. S., Lan, Q., Teras, L. R., Machado, M., Yeager, M., Brooks-Wilson, A. R., Hartge, P. ,... Slager, S. L. (2016). Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. NATURE COMMUNICATIONS, 7 (1), https://doi.org/10.1038/ncomms10933.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258402
    DOI
    10.1038/ncomms10933
    Abstract
    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

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