We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 × 10−10), 2q37.1 (rs13397985, SP140; P = 5.40 × 10−10), 6p25.3 (rs872071, IRF4; P = 1.91 × 10−20), 11q24.1 (rs735665; P = 3.78 × 10−12), 15q23 (rs7176508; P = 4.54 × 10−12) and 19q13.32 (rs11083846, PRKD2; P = 3.96 × 10−9). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.

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Leukaemia Research Fund (LRF) provided principal funding for the study (LRF05001 and 06002). Additional funding was provided by CLL Global Research Foundation, Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund), the Arbib fund and the European Union (CPRB LSHC-CT-2004-503465). D.C.-S. was in receipt of a PhD studentship from the Institute of Cancer Research. We are grateful to M. Yuille for input into our early work on familial CLL. This study made use of genotyping data on the 1958 Birth Cohort. Genotyping data on controls was generated and generously supplied to us by P. Deloukas of the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the data are available from http://www.wtccc.org.uk. We are grateful to all investigators who contributed to the study of acute leukemia, from which phase 3 controls were drawn, to members of the ICLLLC (Supplementary Note online) and to investigators who contributed to NSCCG and GELCAPS, from which phase 1 and 2 controls were drawn. Finally, we are grateful to all the study subjects for their participation.

Author information

Author notes

    • Maria Chiara Di Bernardo
    • , Dalemari Crowther-Swanepoel
    •  & Peter Broderick

    These authors contributed equally to this work.


  1. Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG. UK.

    • Maria Chiara Di Bernardo
    • , Dalemari Crowther-Swanepoel
    • , Peter Broderick
    • , Emily Webb
    • , Gabrielle Sellick
    • , Ruth Wild
    • , Kate Sullivan
    • , Jayaram Vijayakrishnan
    • , Yufei Wang
    • , Alan M Pittman
    •  & Richard S Houlston
  2. Northern Institute for Cancer Research, Paul O'Gorman Building, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK.

    • Nicola J Sunter
    • , Andrew G Hall
    •  & James M Allan
  3. MRC Toxicology Unit, Leicester University, Leicester LE1 9HN, UK.

    • Martin J S Dyer
  4. Section of Haemato-oncology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.

    • Estella Matutes
    • , Claire Dearden
    •  & Daniel Catovsky
  5. Haematological Sciences, Leech Building, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK.

    • Tryfonia Mainou-Fowler
  6. Department of Haematology, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP, UK.

    • Graham H Jackson
  7. Department of Haematology, Queen Elizabeth Hospital, Gateshead, Newcastle-upon-Tyne NE9 6SX, UK.

    • Geoffrey Summerfield
  8. Division of Haematology, University of Liverpool School of Cancer Studies, Liverpool, UK.

    • Robert J Harris
    •  & Andrew R Pettitt
  9. Department of Haematology, Leeds General Infirmary, Leeds LS1 3EX, UK.

    • Peter Hillmen
  10. Department of Haematology, Hull Royal Infirmary, Hull HU3 2JZ, UK.

    • David J Allsup
  11. Hull York Medical School and University of Hull, Hull HU16 5JQ, UK.

    • James R Bailey
  12. Department of Haematology, Birmingham Heartlands Hospital, Birmingham B9, UK.

    • Guy Pratt
  13. Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.

    • Chris Pepper
  14. Cardiff and Vale NHS Trust, Heath Park, Cardiff, CF14 4XW, UK.

    • Chris Fegan


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R.S.H. designed the study with the assistance of G.S.; R.S.H. drafted the manuscript, with substantial contributions from E.W., M.C.D.B. and D.C.-S. M.C.D.B. performed statistical analyses with contributions from E.W. and Y.W. D.C.-S., M.C.D.B. and A.M.P. performed bioinformatics analyses. Phases 1 and 2: P.B. performed laboratory management and oversaw genotyping of cases and controls; D.C.-S., K.S. and J.V. conducted sequencing; D.C.-S. conducted genotyping of cases and controls; R.S.H., G.S., D.C., E.M., C.D. and D.C.-S. developed protocols for recruitment of individuals with CLL and sample acquisition and performed sample collection of cases; members of the ICLLLC consortium carried out ascertainment of familial cases (Supplementary Note). Phase 3: J.M.A. and D.J.A. conceived of the Newcastle-based CLL study. J.M.A. established the study, supervised laboratory management and oversaw genotyping of cases and controls. N.J.S. performed sample management of cases and controls. A.G.H. developed the Newcastle Haematology Biobank, incorporating the Newcastle-based CLL study. T.M.-F., G.H.J., G.S., R.J.H., A.R.P., P.H., D.J.A., J.R.B., G.P., C.P. and C.F. developed protocols for recruitment of individuals with CLL and sample acquisition and performed sample collection of cases. All authors contributed to the final paper.

Corresponding author

Correspondence to Richard S Houlston.

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