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; The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Jyotsna Batra

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
, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
, Jyotsna Batra

Research output: Contribution to journal › Article › Research › peer-review

44 Citations (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.

Original language	English
Article number	1892
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00320-1
Publication status	Published - 1 Dec 2017
Externally published	Yes

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Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibilityFinal published version, 1.79 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., The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, & Batra, J. (2017). Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. Nature Communications, 8(1), 1-11. Article 1892. https://doi.org/10.1038/s41467-017-00320-1

@article{8439e5dc6042445ab022a64a57bca932,

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 \{The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium\} 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 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 Lu, \{Yong Jie\} and Giles, \{Graham G.\} and Kibel, \{Adam S.\} and Ana Vega and Manolis Kogevinas and Penney, \{Kathryn L.\} and Park, \{Jong Y.\} and Stanford, \{Janet L.\} and Cezary Cybulski and Nordestgaard, \{B{\o}rge G.\} and Hermann Brenner and Christiane Maier and Jeri Kim and John, \{Esther M.\} and Teixeira, \{Manuel R.\} and Neuhausen, \{Susan L.\} and \{De Ruyck\}, Kim and Azad Razack and Newcomb, \{Lisa F.\} and Davor Lessel and Radka Kaneva and Nawaid Usmani and Frank Claessens and Townsend, \{Paul A.\} and Dominguez, \{Manuela Gago\} and Roobol, \{Monique J.\} and Florence Menegaux and Per Hoffmann and N{\"o}then, \{Markus M.\} and J{\"o}ckel, \{Karl Heinz\} 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.\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

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

language = "English",

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journal = "Nature Communications",

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Sud, A, Thomsen, H, Law, PJ, Försti, A, Filho, MIDS, Holroyd, A, Broderick, P, Orlando, G, Lenive, O, Wright, L, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium & Batra, J 2017, 'Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility', Nature Communications, vol. 8, no. 1, 1892, pp. 1-11. https://doi.org/10.1038/s41467-017-00320-1

TY - JOUR

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 - The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

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 - 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 - Lu, Yong Jie

AU - Giles, Graham G.

AU - Kibel, Adam S.

AU - Vega, Ana

AU - Kogevinas, Manolis

AU - Penney, Kathryn L.

AU - Park, Jong Y.

AU - Stanford, Janet L.

AU - Cybulski, Cezary

AU - Nordestgaard, Børge G.

AU - Brenner, Hermann

AU - Maier, Christiane

AU - Kim, Jeri

AU - John, Esther M.

AU - Teixeira, Manuel R.

AU - Neuhausen, Susan L.

AU - De Ruyck, Kim

AU - Razack, Azad

AU - Newcomb, Lisa F.

AU - Lessel, Davor

AU - Kaneva, Radka

AU - Usmani, Nawaid

AU - Claessens, Frank

AU - Townsend, Paul A.

AU - Dominguez, Manuela Gago

AU - Roobol, Monique J.

AU - Menegaux, Florence

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.

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.

UR - https://www.scopus.com/pages/publications/85036669716

U2 - 10.1038/s41467-017-00320-1

DO - 10.1038/s41467-017-00320-1

M3 - Article

C2 - 29196614

AN - SCOPUS:85036669716

SN - 2041-1723

VL - 8

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1892

ER -

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

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