Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.
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Authors
Sud, A
Thomsen, H
Orlando, G
Försti, A
Law, PJ
Broderick, P
Cooke, R
Hariri, F
Pastinen, T
Easton, DF
Pharoah, PDP
Dunning, AM
Peto, J
Canzian, F
Eeles, R
Kote-Jarai, Z
Muir, K
Pashayan, N
Campa, D
PRACTICAL Consortium,
Hoffmann, P
Nöthen, MM
Jöckel, K-H
von Strandmann, EP
Swerdlow, AJ
Engert, A
Orr, N
Hemminki, K
Houlston, RS
Thomsen, H
Orlando, G
Försti, A
Law, PJ
Broderick, P
Cooke, R
Hariri, F
Pastinen, T
Easton, DF
Pharoah, PDP
Dunning, AM
Peto, J
Canzian, F
Eeles, R
Kote-Jarai, Z
Muir, K
Pashayan, N
Campa, D
PRACTICAL Consortium,
Hoffmann, P
Nöthen, MM
Jöckel, K-H
von Strandmann, EP
Swerdlow, AJ
Engert, A
Orr, N
Hemminki, K
Houlston, RS
Document Type
Journal Article
Date
2018-11-08
Date Accepted
2018-08-19
Abstract
To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of 7 genome-wide association studies totaling 5325 HL cases and 22 423 control patients. We identify 5 new HL risk loci at 6p21.31 (rs649775; P = 2.11 × 10-10), 6q23.3 (rs1002658; P = 2.97 × 10-8), 11q23.1 (rs7111520; P = 1.44 × 10-11), 16p11.2 (rs6565176; P = 4.00 × 10-8), and 20q13.12 (rs2425752; P = 2.01 × 10-8). Integration of gene expression, histone modification, and in situ promoter capture Hi-C data at the 5 new and 13 known risk loci implicates dysfunction of the germinal center reaction, disrupted T-cell differentiation and function, and constitutive NF-κB activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.
Citation
Blood, 2018, 132 (19), pp. 2040 - 2052
Source Title
Publisher
AMER SOC HEMATOLOGY
ISSN
0006-4971
eISSN
1528-0020
Research Team
Complex Trait Genetics
Aetiological Epidemiology
Cancer Genomics
Molecular & Population Genetics
Oncogenetics
Aetiological Epidemiology
Cancer Genomics
Molecular & Population Genetics
Oncogenetics