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

Amit Sud; Hauke Thomsen; Philip J Law; Asta Försti; Miguel Inacio da Silva Filho; Amy Holroyd; Peter Broderick; Giulia Orlando; Oleg Lenive; Lauren Wright; Rosie Cooke; Douglas Easton; Paul Pharoah; Alison Dunning; Julian Peto; Federico Canzian; Rosalind Eeles; ZSofia Kote-Jarai; Kenneth Muir; Nora Pashayan; Per Hoffmann; Markus M Nöthen; Karl-Heinz Jöckel; Elke Pogge von Strandmann; Tracy Lightfoot; Eleanor Kane; Eve Roman; Annette Lake; Dorothy Montgomery; Ruth F Jarrett; Anthony J Swerdlow; Andreas Engert; Nick Orr; Kari Hemminki; Richard S Houlston; PRACTICAL consortium (Børge Nordestgaard)

doi:10.1038/s41467-017-00320-1

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

Amit Sud, Hauke Thomsen, Philip J Law, Asta Försti, Miguel Inacio da Silva Filho, Amy Holroyd, Peter Broderick, Giulia Orlando, Oleg Lenive, Lauren Wright, Rosie Cooke, Douglas Easton, Paul Pharoah, Alison Dunning, Julian Peto, Federico Canzian, Rosalind Eeles, ZSofia Kote-Jarai, Kenneth Muir, Nora PashayanPer Hoffmann, Markus M Nöthen, Karl-Heinz Jöckel, Elke Pogge von Strandmann, Tracy Lightfoot, Eleanor Kane, Eve Roman, Annette Lake, Dorothy Montgomery, Ruth F Jarrett, Anthony J Swerdlow, Andreas Engert, Nick Orr, Kari Hemminki, Richard S Houlston, PRACTICAL consortium (Børge Nordestgaard)

Klinisk Biokemisk afd.

42 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	8
Udgave nummer	1
Sider (fra-til)	1892
ISSN	2041-1722
DOI	https://doi.org/10.1038/s41467-017-00320-1
Status	Udgivet - 1 dec. 2017

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10.1038/s41467-017-00320-1

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Sud, A., Thomsen, H., Law, P. J., Försti, A., Filho, M. I. D. S., 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, ZS., Muir, K., ... PRACTICAL consortium (Børge Nordestgaard) (2017). Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. Nature Communications, 8(1), 1892. https://doi.org/10.1038/s41467-017-00320-1

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, ZS, Muir, K, Pashayan, N, 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 & PRACTICAL consortium (Børge Nordestgaard) 2017, 'Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility', Nature Communications, bind 8, nr. 1, s. 1892. https://doi.org/10.1038/s41467-017-00320-1

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abstract = "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.",

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author = "Amit Sud and Hauke Thomsen and Law, {Philip J} and Asta F{\"o}rsti and Filho, {Miguel Inacio da Silva} and Amy Holroyd and Peter Broderick and Giulia Orlando and Oleg Lenive and Lauren Wright and Rosie Cooke and Douglas Easton and Paul Pharoah and Alison Dunning and Julian Peto and Federico Canzian and Rosalind Eeles and ZSofia Kote-Jarai and Kenneth Muir and Nora Pashayan and Per Hoffmann and N{\"o}then, {Markus M} and Karl-Heinz J{\"o}ckel and Strandmann, {Elke Pogge von} and Tracy Lightfoot and Eleanor Kane and Eve Roman and Annette Lake and Dorothy Montgomery and Jarrett, {Ruth F} and Swerdlow, {Anthony J} and Andreas Engert and Nick Orr and Kari Hemminki and Houlston, {Richard S} and {PRACTICAL consortium (B{\o}rge Nordestgaard)} and Nordestgaard, {B{\o}rge G.}",

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doi = "10.1038/s41467-017-00320-1",

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T1 - Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

AU - Sud, Amit

AU - Thomsen, Hauke

AU - Law, Philip J

AU - Försti, Asta

AU - Filho, Miguel Inacio da Silva

AU - Holroyd, Amy

AU - Broderick, Peter

AU - Orlando, Giulia

AU - Lenive, Oleg

AU - Wright, Lauren

AU - Cooke, Rosie

AU - Easton, Douglas

AU - Pharoah, Paul

AU - Dunning, Alison

AU - Peto, Julian

AU - Canzian, Federico

AU - Eeles, Rosalind

AU - Kote-Jarai, ZSofia

AU - Muir, Kenneth

AU - Pashayan, Nora

AU - Hoffmann, Per

AU - Nöthen, Markus M

AU - Jöckel, Karl-Heinz

AU - Strandmann, Elke Pogge von

AU - Lightfoot, Tracy

AU - Kane, Eleanor

AU - Roman, Eve

AU - Lake, Annette

AU - Montgomery, Dorothy

AU - Jarrett, Ruth F

AU - Swerdlow, Anthony J

AU - Engert, Andreas

AU - Orr, Nick

AU - Hemminki, Kari

AU - Houlston, Richard S

AU - PRACTICAL consortium (Børge Nordestgaard)

A2 - Nordestgaard, Børge G.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41467-017-00320-1

DO - 10.1038/s41467-017-00320-1

M3 - Journal article

C2 - 29196614

SN - 2041-1722

VL - 8

SP - 1892

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

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