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

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, David J. Allsup, 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 () and Susan Slager ()
Additional contact information
Philip J. Law: The Institute of Cancer Research
Sonja I. Berndt: National Cancer Institute
Helen E. Speedy: The Institute of Cancer Research
Nicola J. Camp: Huntsman Cancer Institute, University of Utah School of Medicine
Georgina P. Sava: The Institute of Cancer Research
Christine F. Skibola: School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham
Amy Holroyd: The Institute of Cancer Research
Vijai Joseph: Memorial Sloan Kettering Cancer Center
Nicola J. Sunter: Northern Institute for Cancer Research, Newcastle University
Alexandra Nieters: Center for Chronic Immunodeficiency, University Medical Center Freiburg
Silvia Bea: Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic
Alain Monnereau: Registre des hémopathies malignes de la Gironde, Institut Bergonié, Inserm U1219 EPICENE
David Martin-Garcia: Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic
Lynn R. Goldin: National Cancer Institute
Guillem Clot: Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic
Lauren R. Teras: Epidemiology Research Program, American Cancer Society
Inés Quintela: Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado (CeGen-PRB2-ISCIII), CIBERER
Brenda M. Birmann: Brigham and Women’s Hospital and Harvard Medical School
Sandrine Jayne: Ernest and Helen Scott Haematological Research Institute, University of Leicester
Wendy Cozen: USC Keck School of Medicine, University of Southern California
Aneela Majid: Ernest and Helen Scott Haematological Research Institute, University of Leicester
Karin E. Smedby: Unit of Clinical Epidemiology, Karolinska Institutet, Hematology Center, Karolinsak University Hospital
Qing Lan: National Cancer Institute
Claire Dearden: The Royal Marsden NHS Foundation Trust
Angela R. Brooks-Wilson: Genome Sciences Centre, BC Cancer Agency
Andrew G. Hall: Northern Institute for Cancer Research, Newcastle University
Mark P. Purdue: National Cancer Institute
Tryfonia Mainou-Fowler: Haematological Sciences, Medical School, Newcastle University
Claire M. Vajdic: Centre for Big Data Research in Health, University of New South Wales
Graham H. Jackson: Royal Victoria Infirmary
Pierluigi Cocco: Clinical and Molecular Medicine, University of Cagliari
Helen Marr: Northern Institute for Cancer Research, Newcastle University
Yawei Zhang: Yale School of Public Health
Tongzhang Zheng: Yale School of Public Health
Graham G. Giles: Cancer Epidemiology Centre, Cancer Council Victoria
Charles Lawrence: Westat
Timothy G. Call: Mayo Clinic
Mark Liebow: Mayo Clinic
Mads Melbye: Statens Serum Institut
Bengt Glimelius: Genetics and Pathology, Science for Life Laboratory, Uppsala University
Larry Mansouri: Genetics and Pathology, Science for Life Laboratory, Uppsala University
Martha Glenn: Huntsman Cancer Institute, University of Utah School of Medicine
Karen Curtin: Huntsman Cancer Institute, University of Utah School of Medicine
W Ryan Diver: Epidemiology Research Program, American Cancer Society
Brian K. Link: Carver College of Medicine, The University of Iowa
Lucia Conde: School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham
Paige M. Bracci: University of California San Francisco
Elizabeth A. Holly: University of California San Francisco
Rebecca D. Jackson: Diabetes and Metabolism, Ohio State University
Lesley F. Tinker: Fred Hutchinson Cancer Research Center
Yolanda Benavente: Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat
Paolo Boffetta: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Paul Brennan: International Agency for Research on Cancer
Marc Maynadie: Registre des Hémopathies Malignes de Côte d’Or, University of Burgundy and Dijon University Hospital
James McKay: International Agency for Research on Cancer
Demetrius Albanes: National Cancer Institute
Stephanie Weinstein: National Cancer Institute
Zhaoming Wang: St Jude Children’s Research Hospital
Neil E. Caporaso: National Cancer Institute
Lindsay M. Morton: National Cancer Institute
Richard K. Severson: Wayne State University
Elio Riboli: School of Public Health, Imperial College London
Paolo Vineis: MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London
Roel C. H. Vermeulen: Institute for Risk Assessment Sciences, Utrecht University
Melissa C. Southey: Genetic Epidemiology Laboratory, University of Melbourne
Roger L. Milne: Cancer Epidemiology Centre, Cancer Council Victoria
Jacqueline Clavel: Epidemiology of Childhood and Adolescent Cancers Group, Inserm, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
Sabine Topka: Memorial Sloan Kettering Cancer Center
John J. Spinelli: Cancer Control Research, BC Cancer Agency
Peter Kraft: Harvard T.H. Chan School of Public Health
Maria Grazia Ennas: University of Cagliari
Geoffrey Summerfield: Queen Elizabeth Hospital
Giovanni M. Ferri: University of Bari
Robert J. Harris: University of Liverpool
Lucia Miligi: Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO)
Andrew R. Pettitt: University of Liverpool
Kari E. North: University of North Carolina at Chapel Hill
David J. Allsup: Queens Centre for Haematology and Oncology, Castle Hill Hospital, Hull and East Yorkshire NHS Trust
Joseph F. Fraumeni: National Cancer Institute
James R. Bailey: Queens Centre for Haematology and Oncology, Castle Hill Hospital, Hull and East Yorkshire NHS Trust
Kenneth Offit: Memorial Sloan Kettering Cancer Center
Guy Pratt: Birmingham Heartlands Hospital
Henrik Hjalgrim: Statens Serum Institut
Chris Pepper: School of Medicine, Cardiff University
Stephen J. Chanock: National Cancer Institute
Chris Fegan: Cardiff and Vale National Health Service Trust, Heath Park
Richard Rosenquist: Genetics and Pathology, Science for Life Laboratory, Uppsala University
Silvia de Sanjose: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai
Angel Carracedo: Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado (CeGen-PRB2-ISCIII), CIBERER
Martin J. S. Dyer: Ernest and Helen Scott Haematological Research Institute, University of Leicester
Daniel Catovsky: The Institute of Cancer Research
Elias Campo: Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic
James R. Cerhan: Mayo Clinic
James M. Allan: Northern Institute for Cancer Research, Newcastle University
Nathanial Rothman: National Cancer Institute
Richard Houlston: The Institute of Cancer Research
Susan Slager: Mayo Clinic

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms14175 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14175

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14175

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().