Genome-wide association study of classical
Hodgkin lymphoma identiﬁes key regulators of
, Hauke Thomsen
, Philip J. Law
, Asta Försti
, Miguel Inacio da Silva Filho
, Amy Holroyd
, Giulia Orlando
, Oleg Lenive
, Lauren Wright
, Rosie Cooke
, Douglas Easton
, Alison Dunning
, Julian Peto
, Federico Canzian
, Rosalind Eeles
, ZSoﬁa Kote-Jarai
, Nora Pashayan
, The PRACTICAL consortium, Per Hoffmann
Markus M. Nöthen
, Karl-Heinz Jöckel
, Elke Pogge von Strandmann
, Tracy Lightfoot
, Eleanor Kane
, Annette Lake
, Dorothy Montgomery
, Ruth F. Jarrett
, Anthony J. Swerdlow
, Nick Orr
, Kari Hemminki
& Richard S. Houlston
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
) and for nodular sclerosis Hodgkin lym-
phoma at 3q28 (rs4459895, P = 9.43 × 10
), 6q23.3 (rs6928977, P = 4.62 × 10
(rs3781093, P = 9.49 × 10
), 13q34 (rs112998813, P = 4.58 × 10
) and 16p13.13
(rs34972832,P= 2.12 × 10
). 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
Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
Division of Molecular Genetic Epidemiology, German
Cancer Research Centre, Heidelberg 69120, Germany.
Centre for Primary Health Care Research, Lund University, Malmö 221 00, Sweden.
Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
Centre for Cancer Genetic Epidemiology,
Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Department of Non-Communicable Disease
Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Genomic Epidemiology Group, German Cancer Research Center
(DKFZ), Heidelberg 69120, Germany.
Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
Institute of Population Health, University of
Manchester, Manchester M1 3BB, UK.
Division of Health Sciences, Warwick Medical School, Warwick University, Warwick CV4 7AL, UK.
Applied Health Research, University College London, London WC1E 7HB, UK.
Department of Biomedicine, Division of Medical Genetics, University of Basel,
Basel 4031, Switzerland.
Institute of Human Genetics, University of Bonn, Bonn 53127, Germany.
Department of Genomics, Life & Brain Center,
University of Bonn, Bonn 53127, Germany.
University of Duisburg–Essen, Essen 47057, Germany.
Department of Internal Medicine, University Hospital of
Cologne, Cologne 50937, Germany.
Department of Health Sciences, University of York, York YO10 5DD, UK.
MRC University of Glasgow Centre for
Virus Research, Glasgow G61 1QH, UK.
Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK.
Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK. Amit Sud and Hauke Thomsen contributed equally to this work.
Kari Hemminki and Richard S. Houlston jointly supervised this work. Correspondence and requests for materials should be addressed to
R.S.H. (email: firstname.lastname@example.org).
A full list of consortium members appears at the end of the paper.