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

Published version
Peer-reviewed

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Authors

Sud, A 
Thomsen, H 
Law, PJ 
Försti, A 
da Silva Filho, MI 

Abstract

Several susceptibility loci for classical Hodgkin lymphoma (cHL) have been reported, however much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies (GWAS), a new GWAS, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all cHL at 6q22.33 (rs9482849, P=1.52 × 10-8) and for nodular sclerosis HL (NSHL) at 3q28 (rs4459895, P=9.43 × 10-17), 6q23.3 (rs6928977, P=4.62 × 10-55 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 NSHL (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity HL (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.

Description

Keywords

Alleles, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DP beta-Chains, HLA-DRB1 Chains, Hodgkin Disease, Humans, Polymorphism, Single Nucleotide

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

8

Publisher

Springer Nature
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)
National Cancer Institute (U19CA148537)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
Cancer Research UK (16563)
Cancer Research UK (10118)
European Commission (223175)
Medical Research Council (G0401527/1)
In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. For further information, please visit the publishr's website.