Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Nat Genet. 2014 Nov;46(11):1233-8. doi: 10.1038/ng.3105. Epub 2014 Sep 28.

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Intramural

MeSH terms

  • Chromosome Mapping
  • Computational Biology
  • European Continental Ancestry Group / genetics*
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Likelihood Functions
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci / genetics