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

Research output: Contribution to journalJournal articleResearchpeer-review

  • James R. Cerhan
  • Sonja I. Berndt
  • Joseph Vijai
  • Hervé Ghesquières
  • James McKay
  • Sophia S. Wang
  • Zhaoming Wang
  • Meredith Yeager
  • Lucia Conde
  • Paul I.W. De Bakker
  • Alexandra Nieters
  • David Cox
  • Laurie Burdett
  • Alain Monnereau
  • Christopher R. Flowers
  • Anneclaire J. De Roos
  • Angela R. Brooks-Wilson
  • Qing Lan
  • Gianluca Severi
  • Jian Gu
  • Rebecca D. Jackson
  • Eleanor Kane
  • Lauren R. Teras
  • Mark P. Purdue
  • Claire M. Vajdic
  • John J. Spinelli
  • Graham G. Giles
  • Demetrius Albanes
  • Rachel S. Kelly
  • Mariagrazia Zucca
  • Kimberly A. Bertrand
  • Anne Zeleniuch-Jacquotte
  • Charles Lawrence
  • Amy Hutchinson
  • Degui Zhi
  • Thomas M. Habermann
  • Brian K. Link
  • Anne J. Novak
  • Ahmet Dogan
  • Yan W. Asmann
  • Mark Liebow
  • Carrie A. Thompson
  • Stephen M. Ansell
  • Thomas E. Witzig
  • George J. Weiner
  • Amelie S. Veron
  • Diana Zelenika
  • Henrik Hjalgrim

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.

Original languageEnglish
JournalNature Genetics
Volume46
Issue number11
Pages (from-to)1233-1238
Number of pages6
ISSN1061-4036
DOIs
Publication statusPublished - 5 Nov 2014
Externally publishedYes

ID: 257835831