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; 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

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, 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

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

18 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
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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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., ... Houlston, R. S. (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, Amit ; Thomsen, Hauke ; Law, Philip J. ; Försti, Asta ; Filho, Miguel Inacio Da Silva ; Holroyd, Amy ; Broderick, Peter ; Orlando, Giulia ; Lenive, Oleg ; Wright, Lauren ; Cooke, Rosie ; Easton, Douglas ; Pharoah, Paul ; Dunning, Alison ; Peto, Julian ; Canzian, Federico ; Eeles, Rosalind ; Kote-Jarai, ZSofia ; Muir, Kenneth ; Pashayan, Nora ; The PRACTICAL consortium ; Nöthen, Markus M. ; Jöckel, Karl Heinz ; Strandmann, Elke Pogge Von ; Lightfoot, Tracy ; Kane, Eleanor ; Roman, Eve ; Lake, Annette ; Montgomery, Dorothy ; Jarrett, Ruth F. ; Swerdlow, Anthony J. ; Engert, Andreas ; Orr, Nick ; Hemminki, Kari ; Houlston, Richard S. / Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. In: Nature Communications. 2017 ; Vol. 8, No. 1.

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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 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 {The PRACTICAL consortium} 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.}",

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

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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, Nöthen, MM, Jöckel, KH, Strandmann, EPV, Lightfoot, T, Kane, E, Roman, E, Lake, A, Montgomery, D, Jarrett, RF, Swerdlow, AJ, Engert, A, Orr, N, Hemminki, K & Houlston, RS 2017, 'Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility', Nature Communications, vol. 8, no. 1, 1892. https://doi.org/10.1038/s41467-017-00320-1

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. / Sud, Amit; Thomsen, Hauke; Law, Philip J.; Försti, Asta; Filho, Miguel Inacio Da Silva; Holroyd, Amy; Broderick, Peter; Orlando, Giulia; Lenive, Oleg; Wright, Lauren; Cooke, Rosie; Easton, Douglas; Pharoah, Paul; Dunning, Alison; Peto, Julian; Canzian, Federico; Eeles, Rosalind; Kote-Jarai, ZSofia; Muir, Kenneth; Pashayan, Nora; The PRACTICAL consortium; Nöthen, Markus M.; Jöckel, Karl Heinz; Strandmann, Elke Pogge Von; Lightfoot, Tracy; Kane, Eleanor; Roman, Eve; Lake, Annette; Montgomery, Dorothy; Jarrett, Ruth F.; Swerdlow, Anthony J.; Engert, Andreas; Orr, Nick; Hemminki, Kari; Houlston, Richard S.

In: Nature Communications, Vol. 8, No. 1, 1892, 01.12.2017.

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

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 - 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

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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 - The PRACTICAL consortium

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.

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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.

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DO - 10.1038/s41467-017-00320-1

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