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Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma

Sud, Amit ; Thomsen, Hauke LU orcid ; Orlando, Giulia ; Försti, Asta LU ; Law, Philip J ; Broderick, Peter ; Cooke, Rosie ; Hariri, Fadi ; Pastinen, Tomi and Easton, Douglas F , et al. (2018) In Blood 132(19). p.2040-2052
Abstract

To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of seven genome-wide association studies totalling 5,325 HL cases and 22,423 controls. We identify five 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 five new and 13 known risk loci implicates dysfunction of the germinal centre reaction, disrupted T-cell differentiation and function, and constitutive NF-κB activation as mechanisms of predisposition. These data... (More)

To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of seven genome-wide association studies totalling 5,325 HL cases and 22,423 controls. We identify five 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 five new and 13 known risk loci implicates dysfunction of the germinal centre 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.

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@article{fb0b8811-1668-41f7-87ff-4c751605c47c,
  abstract     = {{<p>To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of seven genome-wide association studies totalling 5,325 HL cases and 22,423 controls. We identify five 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 five new and 13 known risk loci implicates dysfunction of the germinal centre 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.</p>}},
  author       = {{Sud, Amit and Thomsen, Hauke and Orlando, Giulia and Försti, Asta and Law, Philip J and Broderick, Peter and Cooke, Rosie and Hariri, Fadi and Pastinen, Tomi and Easton, Douglas F and Pharoah, Paul D P and Dunning, Alison M and Peto, Julian and Canzian, Federico and Eeles, Rosalind and Kote-Jarai, ZSofia and Muir, Kenneth and Pashayan, Nora and Campa, Daniele and Hoffmann, Per and Nöthen, Markus M and Jöckel, Karl-Heinz and von Strandmann, Elke Pogge and Swerdlow, Anthony J and Engert, Andreas and Orr, Nick and Hemminki, Kari and Houlston, Richard S}},
  issn         = {{1528-0020}},
  language     = {{eng}},
  number       = {{19}},
  pages        = {{2040--2052}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma}},
  url          = {{http://dx.doi.org/10.1182/blood-2018-06-855296}},
  doi          = {{10.1182/blood-2018-06-855296}},
  volume       = {{132}},
  year         = {{2018}},
}