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

Amit Sud; Hauke Thomsen; Giulia Orlando; Asta Försti; Philip J Law; Peter Broderick; Rosie Cooke; Fadi Hariri; Tomi Pastinen; Douglas F Easton; Paul D P Pharoah; Alison M Dunning; Julian Peto; Federico Canzian; Rosalind Eeles; ZSofia Kote-Jarai; Kenneth Muir; Nora Pashayan; Daniele Campa; Per Hoffmann; Markus M Nöthen; Karl-Heinz Jöckel; Elke Pogge von Strandmann; Anthony J Swerdlow; Andreas Engert; Nick Orr; Kari Hemminki; Richard S Houlston

doi:10.1182/blood-2018-06-855296

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

Amit Sud, Hauke Thomsen, Giulia Orlando, Asta Försti, Philip J Law, Peter Broderick, Rosie Cooke, Fadi Hariri, Tomi Pastinen, Douglas F Easton, Paul D P Pharoah, Alison M Dunning, Julian Peto, Federico Canzian, Rosalind Eeles, ZSofia Kote-Jarai, Kenneth Muir, Nora Pashayan, Daniele Campa, Per HoffmannMarkus M Nöthen, Karl-Heinz Jöckel, Elke Pogge von Strandmann, Anthony J Swerdlow, Andreas Engert, Nick Orr, Kari Hemminki, Richard S Houlston

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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 provide further insights into the genetic susceptibility and biology of HL.

Original language	English
Pages (from-to)	2040-2052
Journal	Blood
Volume	132
Issue number	19
DOIs	https://doi.org/10.1182/blood-2018-06-855296
Publication status	Published - 2018

Subject classification (UKÄ)

Medical Genetics

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10.1182/blood-2018-06-855296

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Sud, A., Thomsen, H., Orlando, G., Försti, A., Law, P. J., Broderick, P., Cooke, R., Hariri, F., Pastinen, T., Easton, D. F., Pharoah, P. D. P., Dunning, A. M., Peto, J., Canzian, F., Eeles, R., Kote-Jarai, ZS., Muir, K., Pashayan, N., Campa, D., ... Houlston, R. S. (2018). Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma. Blood, 132(19), 2040-2052. https://doi.org/10.1182/blood-2018-06-855296

@article{fb0b8811166841f787ff4c751605c47c,

title = "Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma",

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 provide further insights into the genetic susceptibility and biology of HL.",

author = "Amit Sud and Hauke Thomsen and Giulia Orlando and Asta F{\"o}rsti and Law, {Philip J} and Peter Broderick and Rosie Cooke and Fadi Hariri and Tomi Pastinen and Easton, {Douglas F} and Pharoah, {Paul D P} and Dunning, {Alison M} and Julian Peto and Federico Canzian and Rosalind Eeles and ZSofia Kote-Jarai and Kenneth Muir and Nora Pashayan and Daniele Campa and Per Hoffmann and N{\"o}then, {Markus M} and Karl-Heinz J{\"o}ckel and {von Strandmann}, {Elke Pogge} and Swerdlow, {Anthony J} and Andreas Engert and Nick Orr and Kari Hemminki and Houlston, {Richard S}",

note = "Copyright {\textcopyright} 2018 American Society of Hematology.",

year = "2018",

doi = "10.1182/blood-2018-06-855296",

language = "English",

volume = "132",

pages = "2040--2052",

journal = "Blood",

issn = "1528-0020",

publisher = "American Society of Hematology",

number = "19",

}

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, ZS, Muir, K, Pashayan, N, Campa, D, Hoffmann, P, Nöthen, MM, Jöckel, K-H, von Strandmann, EP, Swerdlow, AJ, Engert, A, Orr, N, Hemminki, K & Houlston, RS 2018, 'Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma', Blood, vol. 132, no. 19, pp. 2040-2052. https://doi.org/10.1182/blood-2018-06-855296

TY - JOUR

T1 - Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma

AU - Sud, Amit

AU - Thomsen, Hauke

AU - Orlando, Giulia

AU - Försti, Asta

AU - Law, Philip J

AU - Broderick, Peter

AU - Cooke, Rosie

AU - Hariri, Fadi

AU - Pastinen, Tomi

AU - Easton, Douglas F

AU - Pharoah, Paul D P

AU - Dunning, Alison M

AU - Peto, Julian

AU - Canzian, Federico

AU - Eeles, Rosalind

AU - Kote-Jarai, ZSofia

AU - Muir, Kenneth

AU - Pashayan, Nora

AU - Campa, Daniele

AU - Hoffmann, Per

AU - Nöthen, Markus M

AU - Jöckel, Karl-Heinz

AU - von Strandmann, Elke Pogge

AU - Swerdlow, Anthony J

AU - Engert, Andreas

AU - Orr, Nick

AU - Hemminki, Kari

AU - Houlston, Richard S

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1182/blood-2018-06-855296

DO - 10.1182/blood-2018-06-855296

M3 - Article

C2 - 30194254

SN - 1528-0020

VL - 132

SP - 2040

EP - 2052

JO - Blood

JF - Blood

IS - 19

ER -

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

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