Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility.
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Date
2017-12-01ICR Author
Author
Sud, A
Thomsen, H
Law, PJ
Försti, A
Filho, MIDS
Holroyd, A
Broderick, P
Orlando, G
Lenive, O
Wright, L
Cooke, R
Easton, D
Pharoah, P
Dunning, A
Peto, J
Canzian, F
Eeles, R
Kote-Jarai, Z
Muir, K
Pashayan, N
PRACTICAL consortium,
Hoffmann, P
Nöthen, MM
Jöckel, K-H
Strandmann, EPV
Lightfoot, T
Kane, E
Roman, E
Lake, A
Montgomery, D
Jarrett, RF
Swerdlow, AJ
Engert, A
Orr, N
Hemminki, K
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
PRACTICAL consortium
Humans
Hodgkin Disease
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Alleles
Genome-Wide Association Study
HLA-DRB1 Chains
HLA-DP beta-Chains
Research team
Complex Trait Genetics
Aetiological Epidemiology
Cancer Genomics
Oncogenetics
Language
eng
Date accepted
2017-06-20
License start date
2017-12
Citation
Nature communications, 2017, 8 (1), pp. 1892 - ?
Publisher
NATURE PUBLISHING GROUP