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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Law, Philip J.; Berndt, Sonja I.; Speedy, Helen E.; Camp, Nicola J.; Sava, Georgina P.; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J.; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R.; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E.; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G.; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H.; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W. Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C.H.; Southey, Melissa C.; Milne, Roger L.; Clavel, Jacqueline; Topka, Sabine; Spinelli, John J.; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M.; Harris, Robert J.; Miligi, Lucia; Pettitt, Andrew R.; North, Kari E.; Allsup, David J.; Fraumeni, Joseph F.; Bailey, James R.; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; de Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J. S.; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M.; Rothman, Nathanial; Houlston, Richard; Slager, Susan

Authors

Philip J. Law

Sonja I. Berndt

Helen E. Speedy

Nicola J. Camp

Georgina P. Sava

Christine F. Skibola

Amy Holroyd

Vijai Joseph

Nicola J. Sunter

Alexandra Nieters

Silvia Bea

Alain Monnereau

David Martin-Garcia

Lynn R. Goldin

Guillem Clot

Lauren R. Teras

Inés Quintela

Brenda M. Birmann

Sandrine Jayne

Wendy Cozen

Aneela Majid

Karin E. Smedby

Qing Lan

Claire Dearden

Angela R. Brooks-Wilson

Andrew G. Hall

Mark P. Purdue

Tryfonia Mainou-Fowler

Claire M. Vajdic

Graham H. Jackson

Pierluigi Cocco

Helen Marr

Yawei Zhang

Tongzhang Zheng

Graham G. Giles

Charles Lawrence

Timothy G. Call

Mark Liebow

Mads Melbye

Bengt Glimelius

Larry Mansouri

Martha Glenn

Karen Curtin

W. Ryan Diver

Brian K. Link

Lucia Conde

Paige M. Bracci

Elizabeth A. Holly

Rebecca D. Jackson

Lesley F. Tinker

Yolanda Benavente

Paolo Boffetta

Paul Brennan

Marc Maynadie

James McKay

Demetrius Albanes

Stephanie Weinstein

Zhaoming Wang

Neil E. Caporaso

Lindsay M. Morton

Richard K. Severson

Elio Riboli

Paolo Vineis

Roel C.H. Vermeulen

Melissa C. Southey

Roger L. Milne

Jacqueline Clavel

Sabine Topka

John J. Spinelli

Peter Kraft

Maria Grazia Ennas

Geoffrey Summerfield

Giovanni M. Ferri

Robert J. Harris

Lucia Miligi

Andrew R. Pettitt

Kari E. North

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Dr David Allsup D.J.Allsup@hull.ac.uk
Senior Lecturer in Haematology and Honorary Consultant

Joseph F. Fraumeni

James R. Bailey

Kenneth Offit

Guy Pratt

Henrik Hjalgrim

Chris Pepper

Stephen J. Chanock

Chris Fegan

Richard Rosenquist

Silvia de Sanjose

Angel Carracedo

Martin J. S. Dyer

Daniel Catovsky

Elias Campo

James R. Cerhan

James M. Allan

Nathanial Rothman

Richard Houlston

Susan Slager



Abstract

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10 -13 ), 1q42.13 (rs41271473, P=1.06 × 10 -10 ), 4q24 (rs71597109, P=1.37 × 10 -10 ), 4q35.1 (rs57214277, P=3.69 × 10 -8 ), 6p21.31 (rs3800461, P=1.97 × 10 -8 ), 11q23.2 (rs61904987, P=2.64 × 10 -11 ), 18q21.1 (rs1036935, P=3.27 × 10 -8 ), 19p13.3 (rs7254272, P=4.67 × 10 -8 ) and 22q13.33 (rs140522, P=2.70 × 10 -9 ). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Journal Article Type Article
Publication Date Feb 6, 2017
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Pages 14175
APA6 Citation Law, P. J., Berndt, S. I., Speedy, H. E., Camp, N. J., Sava, G. P., Skibola, C. F., …Slager, S. (2017). Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. Nature communications, 8, 14175. https://doi.org/10.1038/ncomms14175
DOI https://doi.org/10.1038/ncomms14175
Keywords General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
Publisher URL https://www.nature.com/articles/ncomms14175
Copyright Statement This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/





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