Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

  • Amit Sud
  • Hauke Thomsen
  • Philip J Law
  • Asta Försti
  • Miguel Inacio da Silva Filho
  • Amy Holroyd
  • Peter Broderick
  • Giulia Orlando
  • Oleg Lenive
  • Lauren Wright
  • Rosie Cooke
  • Douglas Easton
  • Paul Pharoah
  • Alison Dunning
  • Julian Peto
  • Federico Canzian
  • Rosalind Eeles
  • ZSofia Kote-Jarai
  • Kenneth Muir
  • Nora Pashayan
  • PRACTICAL Consortium
  • Per Hoffmann
  • Markus M Nöthen
  • Karl-Heinz Jöckel
  • Elke Pogge von Strandmann
  • Tracy Lightfoot
  • Eleanor Kane
  • Eve Roman
  • Annette Lake
  • Dorothy Montgomery
  • Ruth F Jarrett
  • Anthony J Swerdlow
  • Andreas Engert
  • Nick Orr
  • Kari Hemminki
  • Richard S Houlston

Abstract

Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10-8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895, P = 9.43 × 10-17), 6q23.3 (rs6928977, P = 4.62 × 10-11), 10p14 (rs3781093, P = 9.49 × 10-13), 13q34 (rs112998813, P = 4.58 × 10-8) and 16p13.13 (rs34972832, P = 2.12 × 10-8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.

Bibliografische Daten

OriginalspracheEnglisch
ISSN2041-1723
DOIs
StatusVeröffentlicht - 01.12.2017
Extern publiziertJa
PubMed 29196614