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, 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 and Richard S. Houlston ()
Additional contact information
Amit Sud: The Institute of Cancer Research
Hauke Thomsen: German Cancer Research Centre
Philip J. Law: The Institute of Cancer Research
Asta Försti: German Cancer Research Centre
Miguel Inacio da Silva Filho: German Cancer Research Centre
Amy Holroyd: The Institute of Cancer Research
Peter Broderick: The Institute of Cancer Research
Giulia Orlando: The Institute of Cancer Research
Oleg Lenive: The Institute of Cancer Research
Lauren Wright: The Institute of Cancer Research
Rosie Cooke: The Institute of Cancer Research
Douglas Easton: University of Cambridge
Paul Pharoah: University of Cambridge
Alison Dunning: University of Cambridge
Julian Peto: London School of Hygiene and Tropical Medicine
Federico Canzian: Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
Rosalind Eeles: The Institute of Cancer Research
ZSofia Kote-Jarai: The Institute of Cancer Research
Kenneth Muir: University of Manchester
Nora Pashayan: University of Cambridge
Per Hoffmann: University of Basel
Markus M. Nöthen: University of Bonn
Karl-Heinz Jöckel: University of Duisburg–Essen
Elke Pogge von Strandmann: University Hospital of Cologne
Tracy Lightfoot: University of York
Eleanor Kane: University of York
Eve Roman: University of York
Annette Lake: MRC University of Glasgow Centre for Virus Research
Dorothy Montgomery: MRC University of Glasgow Centre for Virus Research
Ruth F. Jarrett: MRC University of Glasgow Centre for Virus Research
Anthony J. Swerdlow: The Institute of Cancer Research
Andreas Engert: University Hospital of Cologne
Nick Orr: The Institute of Cancer Research
Kari Hemminki: German Cancer Research Centre
Richard S. Houlston: The Institute of Cancer Research

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00320-1

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