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

Law, Philip J; Berndt, Sonja I; Speedy, Helen E; Camp, Nicola J; Sava, Georgina P; Skibola, Christine F; Holroyd, Amy; Joseph, Vijai et al. · Nat Commun · 2017

meta_analysis · Level I

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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<sup>-13</sup>), 1q42.13 (rs41271473, P=1.06 × 10<sup>-10</sup>), 4q24 (rs71597109, P=1.37 × 10<sup>-10</sup>), 4q35.1 (rs57214277, P=3.69 × 10<sup>-8</sup>), 6p21.31 (rs3800461, P=1.97 × 10<sup>-8</sup>), 11q23.2 (rs61904987, P=2.64 × 10<sup>-11</sup>), 18q21.1 (rs1036935, P=3.27 × 10<sup>-8</sup>), 19p13.3 (rs7254272, P=4.67 × 10<sup>-8</sup>) and 22q13.33 (rs140522, P=2.70 × 10<sup>-9</sup>). 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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