A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.

Helen E Speedy, Maria Chiara Di Bernardo, Georgina P Sava, Martin J S Dyer, Amy Holroyd, Yufei Wang, Nicola J Sunter, Larry Mansouri, Gunnar Juliusson, Karin E Smedby, Göran Roos, Sandrine Jayne, Aneela Majid, Claire Dearden, Andrew G Hall, Tryfonia Mainou-Fowler, Graham H Jackson, Geoffrey Summerfield, Robert J Harris, Andrew R PettittDavid J Allsup, James R Bailey, Guy Pratt, Chris Pepper, Chris Fegan, Richard Rosenquist, Daniel Catovsky, James M Allan, Richard S Houlston

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    141 Citations (SciVal)

    Abstract

    Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.
    Original languageEnglish
    Pages (from-to)56
    JournalNature Genetics
    Volume46
    Issue number1
    DOIs
    Publication statusPublished - 2014

    Subject classification (UKÄ)

    • Cell and Molecular Biology

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