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; The Practical Consortium; Brian E. Henderson; Christopher A. Haiman; Sara Benlloch; Fredrick R. Schumacher; Ali Amin Al Olama; Sonja I. Berndt; David V. Conti; Fredrik Wiklund; Stephen Chanock; Victoria L. Stevens; Catherine M. Tangen; Jyotsna Batra; Judith Clements; Henrik Gronberg; Johanna Schleutker; Demetrius Albanes; Stephanie Weinstein; Alicja Wolk; Catharine West; Lorelei Mucci; Géraldine Cancel-Tassin; Stella Koutros; Karina Dalsgaard Sorensen; Lovise Maehle; David E. Neal; Ruth C. Travis; Robert J. Hamilton; Sue Ann Ingles; Barry Rosenstein; Børge G. 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 PashayanThe Practical Consortium, Brian E. Henderson, Christopher A. Haiman, Sara Benlloch, Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen Chanock, Victoria L. Stevens, Catherine M. Tangen, Jyotsna Batra, Judith Clements, Henrik Gronberg, Johanna Schleutker, Demetrius Albanes, Stephanie Weinstein, Alicja Wolk, Catharine West, Lorelei Mucci, Géraldine Cancel-Tassin, Stella Koutros, Karina Dalsgaard Sorensen, Lovise Maehle, David E. Neal, Ruth C. Travis, Robert J. Hamilton, Sue Ann Ingles, Barry Rosenstein, Børge G. Nordestgaard

Department of Clinical Medicine

19 Citations (Scopus)

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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.

Original language	English
Article number	1892
Journal	Nature Communications
Volume	8
Number of pages	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-017-00320-1
Publication status	Published - 2017

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Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibilityFinal published version, 2.3 MBLicence: CC BY

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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., ... Nordestgaard, B. G. (2017). Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. Nature Communications, 8, [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, The Practical Consortium, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Olama, AAA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Schleutker, J, Albanes, D, Weinstein, S, Wolk, A, West, C, Mucci, L, Cancel-Tassin, G, Koutros, S, Sorensen, KD, Maehle, L, Neal, DE, Travis, RC, Hamilton, RJ, Ingles, SA, Rosenstein, B & Nordestgaard, BG 2017, 'Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility', Nature Communications, vol. 8, 1892. https://doi.org/10.1038/s41467-017-00320-1

@article{c7601a6de6054e9aaec81165c8629319,

title = "Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility",

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.",

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 {The Practical Consortium} and Henderson, {Brian E.} and Haiman, {Christopher A.} and Sara Benlloch and Schumacher, {Fredrick R.} and Olama, {Ali Amin Al} and Berndt, {Sonja I.} and Conti, {David V.} and Fredrik Wiklund and Stephen Chanock and Stevens, {Victoria L.} and Tangen, {Catherine M.} and Jyotsna Batra and Judith Clements and Henrik Gronberg and Johanna Schleutker and Demetrius Albanes and Stephanie Weinstein and Alicja Wolk and Catharine West and Lorelei Mucci and G{\'e}raldine Cancel-Tassin and Stella Koutros and Sorensen, {Karina Dalsgaard} and Lovise Maehle and Neal, {David E.} and Travis, {Ruth C.} and Hamilton, {Robert J.} and Ingles, {Sue Ann} and Barry Rosenstein and Nordestgaard, {B{\o}rge G.}",

year = "2017",

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

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

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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 - The Practical Consortium

AU - Henderson, Brian E.

AU - Haiman, Christopher A.

AU - Benlloch, Sara

AU - Schumacher, Fredrick R.

AU - Olama, Ali Amin Al

AU - Berndt, Sonja I.

AU - Conti, David V.

AU - Wiklund, Fredrik

AU - Chanock, Stephen

AU - Stevens, Victoria L.

AU - Tangen, Catherine M.

AU - Batra, Jyotsna

AU - Clements, Judith

AU - Gronberg, Henrik

AU - Schleutker, Johanna

AU - Albanes, Demetrius

AU - Weinstein, Stephanie

AU - Wolk, Alicja

AU - West, Catharine

AU - Mucci, Lorelei

AU - Cancel-Tassin, Géraldine

AU - Koutros, Stella

AU - Sorensen, Karina Dalsgaard

AU - Maehle, Lovise

AU - Neal, David E.

AU - Travis, Ruth C.

AU - Hamilton, Robert J.

AU - Ingles, Sue Ann

AU - Rosenstein, Barry

AU - Nordestgaard, Børge G.

PY - 2017

Y1 - 2017

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.

UR - https://www.nature.com/articles/s41467-018-08105-w

U2 - 10.1038/s41467-017-00320-1

DO - 10.1038/s41467-017-00320-1

M3 - Journal article

C2 - 29196614

AN - SCOPUS:85036669716

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 1892

ER -

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

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