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

Research output: Contribution to journalArticle

  • External authors:
  • 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
  • Nora Pashayan
  • Brian E. Henderson
  • Christopher A. Haiman
  • Sara Benlloch
  • Fredrick R. Schumacher
  • Ali Amin Al Olama
  • Sonja I. Berndt
  • David V. Conti
  • Fredrik Wiklund
  • Stephen Chanock
  • Victoria L. Stevens
  • Catherine M. Tangen
  • Jyotsna Batra
  • Judith Clements
  • Henrik Gronberg
  • Johanna Schleutker
  • Demetrius Albanes
  • Stephanie Weinstein
  • Alicja Wolk
  • Lorelei Mucci
  • Géraldine Cancel-Tassin
  • Stella Koutros
  • Karina Dalsgaard Sorensen
  • Lovise Maehle
  • David E. Neal
  • Ruth C. Travis
  • Robert J. Hamilton
  • Sue Ann Ingles
  • Barry Rosenstein
  • Yong Jie Lu
  • Graham G. Giles
  • Adam S. Kibel
  • Ana Vega
  • Manolis Kogevinas
  • Kathryn L. Penney
  • Jong Y. Park
  • Janet L. Stanford
  • Cezary Cybulski
  • Børge G. Nordestgaard
  • Hermann Brenner
  • Christiane Maier
  • Jeri Kim
  • Esther M. John
  • Manuel R. Teixeira
  • Susan L. Neuhausen
  • Kim De Ruyck
  • Azad Razack
  • Lisa F. Newcomb
  • Davor Lessel
  • Radka Kaneva
  • Nawaid Usmani
  • Frank Claessens
  • Manuela Gago Dominguez
  • Monique J. Roobol
  • Florence Menegaux
  • 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.

Bibliographical metadata

Original languageEnglish
Article number1892
JournalNature Communications
Volume8
Issue number1
Early online date1 Dec 2017
DOIs
Publication statusPublished - 2017