Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Nat Commun. 2016 Mar 9:7:10933. doi: 10.1038/ncomms10933.

Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Bcl-2-Like Protein 11
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Membrane Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins / genetics
  • Serpins / genetics
  • T-Box Domain Proteins / genetics
  • White People / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BANK1 protein, human
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • CSRNP1 protein, human
  • EOMES protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Serpins
  • T-Box Domain Proteins
  • serpin B6

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