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

Nat Commun. 2017 Feb 6:8:14175. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibody Formation / genetics*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Young Adult

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