A Genome-Wide Association Study Identifies Multiple Susceptibility Loci for Chronic Lymphocytic Leukemia

Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Chromosomes, Human, Pair 3
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Recombination, Genetic
  • Telomere-Binding Proteins / genetics

Substances

  • CLPTM1L protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • POT1 protein, human
  • Telomere-Binding Proteins