Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia (original) (raw)

References

1. Albright, F., Teerlink, C., Werner, T.L. & Cannon-Albright, L.A. Significant evidence for a heritable contribution to cancer predisposition: a review of cancer familiality by site. BMC Cancer 12, 138 (2012).
   Article PubMed PubMed Central Google Scholar
2. Goldin, L.R., Bjorkholm, M., Kristinsson, S.Y., Turesson, I. & Landgren, O. Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia. Haematologica 94, 647–653 (2009).
   Article PubMed PubMed Central Google Scholar
3. Di Bernardo, M.C. et al. A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Nat. Genet. 40, 1204–1210 (2008).
   Article CAS PubMed Google Scholar
4. Crowther-Swanepoel, D. et al. Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk. Nat. Genet. 42, 132–136 (2010).
   Article CAS PubMed PubMed Central Google Scholar
5. Slager, S.L. et al. Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. Blood 117, 1911–1916 (2011).
   Article CAS PubMed PubMed Central Google Scholar
6. Slager, S.L. et al. Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia. Blood 120, 843–846 (2012).
   Article CAS PubMed PubMed Central Google Scholar
7. Park, J.H. et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat. Genet. 42, 570–575 (2010).
   Article CAS PubMed PubMed Central Google Scholar
8. Wang, Z. et al. Improved imputation of common and uncommon SNPs with a new reference set. Nat. Genet. 44, 6–7 (2012).
   Article CAS Google Scholar
9. Conde, L. et al. Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32. Nat. Genet. 42, 661–664 (2010).
   Article CAS PubMed PubMed Central Google Scholar
10. 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010).
11. Howie, B.N., Donnelly, P. & Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 5, e1000529 (2009).
    Article PubMed PubMed Central CAS Google Scholar
12. Crowther-Swanepoel, D. et al. Common genetic variation at 15q25.2 impacts on chronic lymphocytic leukaemia risk. Br. J. Haematol. 154, 229–233 (2011).
    Article PubMed Google Scholar
13. Rafnar, T. et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat. Genet. 41, 221–227 (2009).
    Article CAS PubMed PubMed Central Google Scholar
14. Shete, S. et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat. Genet. 41, 899–904 (2009).
    Article CAS PubMed PubMed Central Google Scholar
15. McKay, J.D. et al. Lung cancer susceptibility locus at 5p15.33. Nat. Genet. 40, 1404–1406 (2008).
    Article CAS PubMed PubMed Central Google Scholar
16. Wang, Y. et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat. Genet. 40, 1407–1409 (2008).
    Article CAS PubMed PubMed Central Google Scholar
17. Petersen, G.M. et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet. 42, 224–228 (2010).
    Article CAS PubMed PubMed Central Google Scholar
18. Haiman, C.A. et al. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer. Nat. Genet. 43, 1210–1214 (2011).
    Article CAS PubMed PubMed Central Google Scholar
19. Kote-Jarai, Z. et al. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat. Genet. 43, 785–791 (2011).
    Article CAS PubMed PubMed Central Google Scholar
20. Sheng, X. et al. TERT polymorphisms modify the risk of acute lymphoblastic leukemia in Chinese children. Carcinogenesis 34, 228–235 (2013).
    Article CAS PubMed Google Scholar
21. Yang, J. et al. Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 42, 565–569 (2010).
    Article CAS PubMed PubMed Central Google Scholar
22. Lee, S.H., Wray, N.R., Goddard, M.E. & Visscher, P.M. Estimating missing heritability for disease from genome-wide association studies. Am. J. Hum. Genet. 88, 294–305 (2011).
    Article PubMed PubMed Central CAS Google Scholar
23. Fisher, G.H. et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81, 935–946 (1995).
    Article CAS PubMed Google Scholar
24. Drappa, J., Vaishnaw, A.K., Sullivan, K.E., Chu, J.L. & Elkon, K.B. Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N. Engl. J. Med. 335, 1643–1649 (1996).
    Article CAS PubMed Google Scholar
25. Straus, S.E. et al. The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. Blood 98, 194–200 (2001).
    Article CAS PubMed Google Scholar
26. Baseggio, L. et al. In non-follicular lymphoproliferative disorders, IGH/BCL2-fusion is not restricted to chronic lymphocytic leukaemia. Br. J. Haematol. 158, 489–498 (2012).
    Article CAS PubMed Google Scholar
27. Cleary, M.L., Smith, S.D. & Sklar, J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47, 19–28 (1986).
    Article CAS PubMed Google Scholar
28. Reshmi, G. et al. C-T variant in a miRNA target site of BCL2 is associated with increased risk of human papilloma virus related cervical cancer—an in silico approach. Genomics 98, 189–193 (2011).
    Article CAS PubMed Google Scholar
29. Cheung, V.G. et al. Polymorphic _cis_- and _trans_-regulation of human gene expression. PLoS Biol. 8, e1000480 (2010).
    Article PubMed PubMed Central CAS Google Scholar
30. Strasser, A., Harris, A.W. & Cory, S. E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells. Oncogene 8, 1–9 (1993).
    CAS PubMed Google Scholar
31. Wensveen, F.M. et al. BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation. Blood 119, 1440–1449 (2012).
    Article CAS PubMed Google Scholar
32. Smit, L.A. et al. Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. Blood 109, 1660–1668 (2007).
    Article CAS PubMed Google Scholar
33. Morales, A.A. et al. Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells. Leukemia 18, 41–47 (2004).
    Article CAS PubMed Google Scholar
34. Labi, V. et al. Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation–induced thymic lymphoma development. J. Exp. Med. 205, 641–655 (2008).
    Article CAS PubMed PubMed Central Google Scholar
35. Crowther-Swanepoel, D. et al. Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk. Br. J. Haematol. 150, 473–479 (2010).
    PubMed Google Scholar
36. Lan, Q. et al. Genetic susceptibility for chronic lymphocytic leukemia among Chinese in Hong Kong. Eur. J. Haematol. 85, 492–495 (2010).
    Article PubMed PubMed Central Google Scholar
37. Nieters, A. et al. PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium. Blood 120, 4645–4648 (2012).
    Article CAS PubMed PubMed Central Google Scholar
38. Egle, A., Harris, A.W., Bouillet, P. & Cory, S. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc. Natl. Acad. Sci. USA 101, 6164–6169 (2004).
    Article CAS PubMed PubMed Central Google Scholar
39. Kelly, J.L. et al. Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma. Cancer Epidemiol. Biomarkers Prev. 19, 2847–2858 (2010).
    Article CAS PubMed PubMed Central Google Scholar
40. Cox, A. et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat. Genet. 39, 352–358 (2007).
    Article CAS PubMed Google Scholar
41. Abnet, C.C. et al. Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies. Hum. Mol. Genet. 21, 2132–2141 (2012).
    Article CAS PubMed PubMed Central Google Scholar
42. Barrett, J.H. et al. Genome-wide association study identifies three new melanoma susceptibility loci. Nat. Genet. 43, 1108–1113 (2011).
    Article CAS PubMed PubMed Central Google Scholar
43. Enjuanes, A. et al. Genetic variants in apoptosis and immunoregulation-related genes are associated with risk of chronic lymphocytic leukemia. Cancer Res. 68, 10178–10186 (2008).
    Article CAS PubMed Google Scholar
44. Lan, Q. et al. Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma. Carcinogenesis 28, 823–827 (2007).
    Article CAS PubMed Google Scholar
45. Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409–414 (2003).
    Article CAS PubMed Google Scholar
46. Gutierrez, A. Jr. et al. LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis. Blood 116, 2975–2983 (2010).
    Article CAS PubMed PubMed Central Google Scholar
47. Cunnington, M.S., Santibanez Koref, M., Mayosi, B.M., Burn, J. & Keavney, B. Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression. PLoS Genet. 6, e1000899 (2010).
    Article PubMed PubMed Central CAS Google Scholar
48. Koufos, A. et al. Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am. J. Hum. Genet. 44, 711–719 (1989).
    CAS PubMed PubMed Central Google Scholar
49. Weksberg, R., Shuman, C. & Beckwith, J.B. Beckwith-Wiedemann syndrome. Eur. J. Hum. Genet. 18, 8–14 (2010).
    Article PubMed Google Scholar
50. Morton, L.M. et al. Proposed classification of lymphoid neoplasms for epidemiologic research from the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph). Blood 110, 695–708 (2007).
    Article CAS PubMed PubMed Central Google Scholar
51. Turner, J.J. et al. InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions. Blood 116, e90–e98 (2010).
    Article CAS PubMed PubMed Central Google Scholar
52. Pritchard, J.K., Stephens, M. & Donnelly, P. Inference of population structure using multilocus genotype data. Genetics 155, 945–959 (2000).
    CAS PubMed PubMed Central Google Scholar
53. Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).
    Article CAS PubMed Google Scholar
54. Ward, L.D. & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40, D930–D934 (2012).
    Article CAS PubMed Google Scholar
55. Dixon, A.L. et al. A genome-wide association study of global gene expression. Nat. Genet. 39, 1202–1207 (2007).
    Article CAS PubMed Google Scholar
56. Stranger, B.E. et al. Population genomics of human gene expression. Nat. Genet. 39, 1217–1224 (2007).
    Article CAS PubMed PubMed Central Google Scholar
57. Pharoah, P.D. et al. Polygenic susceptibility to breast cancer and implications for prevention. Nat. Genet. 31, 33–36 (2002).
    Article CAS PubMed Google Scholar
58. Yang, J., Lee, S.H., Goddard, M.E. & Visscher, P.M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011).
    Article CAS PubMed PubMed Central Google Scholar
59. Fearnhead, P. SequenceLDhot: detecting recombination hotspots. Bioinformatics 22, 3061–3066 (2006).
    Article CAS PubMed Google Scholar
60. Fearnhead, P., Harding, R.M., Schneider, J.A., Myers, S. & Donnelly, P. Application of coalescent methods to reveal fine-scale rate variation and recombination hotspots. Genetics 167, 2067–2081 (2004).
    Article CAS PubMed PubMed Central Google Scholar
61. Li, N. & Stephens, M. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. Genetics 165, 2213–2233 (2003).
    CAS PubMed PubMed Central Google Scholar
62. Crawford, D.C. et al. Evidence for substantial fine-scale variation in recombination rates across the human genome. Nat. Genet. 36, 700–706 (2004).
    Article CAS PubMed Google Scholar
63. Luna, A. & Nicodemus, K.K. snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package. Bioinformatics 23, 774–776 (2007).
    Article CAS PubMed Google Scholar

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Acknowledgements

We thank C. Allmer, E. Angelucci, A. Bigelow, I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, J.M. Conners, D. Connley, M. Cornelis, K. Corsano, C. Dalley, D. Cox, H. Cramp, R. Cutting, H. Dykes, L. Ershler, A. Gabbas, R.P. Gallagher, R.D. Gascoyne, P. Hui, L. Irish, L. Jacobus, S. Kaul, J. Lunde, M. McAdams, R. Montalvan, M. Rais, T. Rattle, L. Rigacci, K. Snyder, G. Specchia, M. Stagner, P. Taylor, G. Thomas, C. Tornow, G. Wood, M. Yang and M. Zucca for their assistance. The overall GWAS project was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, NCI, US National Institutes of Health. A full list of acknowledgments is provided in the Supplementary Note.

Author information

Author notes

1. Sonja I Berndt, Christine F Skibola, Vijai Joseph, Nicola J Camp and Alexandra Nieters: These authors contributed equally to this work.
2. Silvia de Sanjose, Henrik Hjalgrim, James R Cerhan, Stephen J Chanock, Nathaniel Rothman and Susan L Slager: These authors jointly directed this work.

Authors and Affiliations

1. Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Bethesda, Maryland, USA
   Sonja I Berndt, Qing Lan, Nilanjan Chatterjee, Charles C Chung, Patricia Hartge, Mark P Purdue, Lynn R Goldin, Neil E Caporaso, Martha S Linet, Lindsay M Morton, Demetrius Albanes, Stephanie Weinstein, Joshua Sampson, Joseph F Fraumeni Jr, Stephen J Chanock & Nathaniel Rothman
2. Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USA
   Christine F Skibola, Lucia Conde, Jacques Riby & Martyn T Smith
3. School of Public Health, University of Alabama, Birmingham, Alabama, USA
   Christine F Skibola & Lucia Conde
4. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
   Vijai Joseph, Kenneth Offit, Andrew Zelenetz & Robert J Klein
5. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
   Nicola J Camp, Karen Curtin, Lisa A Cannon-Albright & Brandt Jones
6. Center of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Hesse, Germany
   Alexandra Nieters
7. Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, NCI, Bethesda, Maryland, USA
   Zhaoming Wang, Charles C Chung, Meredith Yeager, Laurie Burdette, Jeffrey Yuenger, Amy Hutchinson & Kevin B Jacobs
8. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
   Wendy Cozen
9. U1018 EQ6, Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif Cedex, France
   Alain Monnereau & Jacqueline Clavel
10. Registre des Hémopathies Malignes de la Gironde, Institut Bergonié, Bordeaux Cedex, France
    Alain Monnereau
11. Division of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California, USA
    Sophia S Wang
12. Medical Research Council–Health Protection Agency (MRC-HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
    Rachel S Kelly & Paolo Vineis
13. Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA
    Lauren R Teras & W Ryan Diver
14. Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada
    Angela R Brooks-Wilson
15. Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
    Angela R Brooks-Wilson
16. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Brenda M Birmann, Kimberly A Bertrand, Francine Laden & Edward Giovannucci
17. Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
    Bruce K Armstrong & Anne Kricker
18. Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari, Italy
    Pierluigi Cocco
19. Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
    Yawei Zhang & Tongzhang Zheng
20. Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia
    Gianluca Severi & Graham G Giles
21. Department of Population Health, New York University School of Medicine, New York, New York, USA
    Anne Zeleniuch-Jacquotte
22. Health Studies Sector, Westat, Rockville, Maryland, USA
    Charles Lawrence
23. Division of Hematology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Timothy G Call & Neil E Kay
24. Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Tait D Shanafelt & Anne J Novak
25. Division of General Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Mark Liebow
26. Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Alice H Wang, Kari G Rabe, Sara J Achenbach, Celine M Vachon, Aaron D Norman, James R Cerhan & Susan L Slager
27. Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
    Karin E Smedby
28. Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
    Karin E Smedby & Bengt Glimelius
29. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Hans-Olov Adami & Elisabete Weiderpass
30. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    Hans-Olov Adami, Dimitrios Trichopoulos, Kimberly A Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft & Liming Liang
31. Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
    Mads Melbye & Henrik Hjalgrim
32. Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden
    Bengt Glimelius
33. Center for Epidemiology and Computational Biology, Health Sciences, Exponent, Inc., Menlo Park, California, USA
    Ellen T Chang
34. Department of Health Research and Policy, Division of Epidemiology, Stanford University School of Medicine, Stanford, California, USA
    Ellen T Chang
35. Department of Internal Medicine, Huntsman Cancer Institute, Salt Lake City, Utah, USA
    Martha Glenn
36. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, USA
    Lisa A Cannon-Albright
37. Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA
    Brian K Link & George J Weiner
38. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
    Paige M Bracci & Elizabeth A Holly
39. Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio, USA
    Rebecca D Jackson
40. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Lesley F Tinker & Anneclaire J De Roos
41. Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain
    Yolanda Benavente & Silvia de Sanjose
42. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
    Yolanda Benavente, María-Dolores Chirlaque & Silvia de Sanjose
43. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany
    Nikolaus Becker & Rudolph Kaaks
44. The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
    Paolo Boffetta
45. Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon, France
    Paul Brennan
46. Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
    Lenka Foretova
47. EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France
    Marc Maynadie
48. Genetic Cancer Susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon, France
    James McKay
49. School of Nursing and Human Sciences, Dublin City University, Dublin, Leinster, Ireland
    Anthony Staines
50. Department of Epidemiology, M.D. Anderson Cancer Center, Houston, Texas, USA
    Sara S Strom
51. Department of Medicine, Duke University and VA Medical Centers, Durham, North Carolina, USA
    Mark C Lanasa & J Brice Weinberg
52. Division of Epidemiology and Clinical Research, University of Minnesota, Minneapolis, Minnesota, USA
    Logan G Spector
53. Division of Hematology and Oncology, College of Medicine, Mayo Clinic, Phoenix, Arizona, USA
    Jose F Leis
54. Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Julie M Cunningham
55. Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota, USA
    Vicki A Morrison
56. Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA
    Richard K Severson
57. School of Public Health, Imperial College London, London, UK
    Elio Riboli
58. Human Genetics Foundation, Turin, Italy
    Paolo Vineis
59. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
    Dimitrios Trichopoulos
60. Hellenic Health Foundation, Athens, Greece
    Dimitrios Trichopoulos
61. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
    Giovanna Masala
62. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Breivika, Norway
    Elisabete Weiderpass
63. Cancer Registry of Norway, Oslo, Norway
    Elisabete Weiderpass
64. Folkhalsan Research Center, Samfundet Folkhalsan, Helsinki, Finland
    Elisabete Weiderpass
65. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain
    María-Dolores Chirlaque
66. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
    Roel C H Vermeulen
67. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
    Roel C H Vermeulen
68. Cancer Epidemiology Unit, University of Oxford, Oxford, UK
    Ruth C Travis
69. Department of Chronic Disease and Prevention, National Institute for Health and Welfare, Helsinki, Finland
    Jarmo Virtamo
70. Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA
    Theodore R Holford
71. Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Robert J Klein
72. Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada
    John J Spinelli
73. Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
    Francine Laden
74. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
    Edward Giovannucci
75. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
    Peter Kraft & Liming Liang
76. Department of Pathology, Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
    Jenny Turner
77. Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, Australia
    Jenny Turner
78. Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
    Claire M Vajdic
79. Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari, Italy
    Maria Grazia Ennas
80. Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
    Giovanni M Ferri
81. Environmental and Occupational Epidemiology Unit, ISPO, Florence, Italy
    Lucia Miligi
82. Department of Health Sciences, Epidemiology and Genetics Unit, University of York, York, UK
    Simon Crouch
83. Dongguk University-Seoul, Seoul, South Korea
    Ju-Hyun Park
84. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
    Kari E North
85. Department of Oncology, University of Sheffield, Sheffield, UK
    Angela Cox & John A Snowden
86. Department of Haematology, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, UK
    John A Snowden & Josh Wright
87. Genomic Medicine Group Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), University of Santiago de Compostela, Santiago de Compostela, Spain
    Angel Carracedo
88. Department of Biochemistry and Molecular Biology, Institute of Oncology, University of Oviedo, Oviedo, Spain
    Carlos Lopez-Otin
89. August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
    Silvia Bea, Itziar Salaverria, David Martin-Garcia & Elias Campo

Authors

1. Sonja I Berndt
2. Christine F Skibola
3. Vijai Joseph
4. Nicola J Camp
5. Alexandra Nieters
6. Zhaoming Wang
7. Wendy Cozen
8. Alain Monnereau
9. Sophia S Wang
10. Rachel S Kelly
11. Qing Lan
12. Lauren R Teras
13. Nilanjan Chatterjee
14. Charles C Chung
15. Meredith Yeager
16. Angela R Brooks-Wilson
17. Patricia Hartge
18. Mark P Purdue
19. Brenda M Birmann
20. Bruce K Armstrong
21. Pierluigi Cocco
22. Yawei Zhang
23. Gianluca Severi
24. Anne Zeleniuch-Jacquotte
25. Charles Lawrence
26. Laurie Burdette
27. Jeffrey Yuenger
28. Amy Hutchinson
29. Kevin B Jacobs
30. Timothy G Call
31. Tait D Shanafelt
32. Anne J Novak
33. Neil E Kay
34. Mark Liebow
35. Alice H Wang
36. Karin E Smedby
37. Hans-Olov Adami
38. Mads Melbye
39. Bengt Glimelius
40. Ellen T Chang
41. Martha Glenn
42. Karen Curtin
43. Lisa A Cannon-Albright
44. Brandt Jones
45. W Ryan Diver
46. Brian K Link
47. George J Weiner
48. Lucia Conde
49. Paige M Bracci
50. Jacques Riby
51. Elizabeth A Holly
52. Martyn T Smith
53. Rebecca D Jackson
54. Lesley F Tinker
55. Yolanda Benavente
56. Nikolaus Becker
57. Paolo Boffetta
58. Paul Brennan
59. Lenka Foretova
60. Marc Maynadie
61. James McKay
62. Anthony Staines
63. Kari G Rabe
64. Sara J Achenbach
65. Celine M Vachon
66. Lynn R Goldin
67. Sara S Strom
68. Mark C Lanasa
69. Logan G Spector
70. Jose F Leis
71. Julie M Cunningham
72. J Brice Weinberg
73. Vicki A Morrison
74. Neil E Caporaso
75. Aaron D Norman
76. Martha S Linet
77. Anneclaire J De Roos
78. Lindsay M Morton
79. Richard K Severson
80. Elio Riboli
81. Paolo Vineis
82. Rudolph Kaaks
83. Dimitrios Trichopoulos
84. Giovanna Masala
85. Elisabete Weiderpass
86. María-Dolores Chirlaque
87. Roel C H Vermeulen
88. Ruth C Travis
89. Graham G Giles
90. Demetrius Albanes
91. Jarmo Virtamo
92. Stephanie Weinstein
93. Jacqueline Clavel
94. Tongzhang Zheng
95. Theodore R Holford
96. Kenneth Offit
97. Andrew Zelenetz
98. Robert J Klein
99. John J Spinelli
100. Kimberly A Bertrand
101. Francine Laden
102. Edward Giovannucci
103. Peter Kraft
104. Anne Kricker
105. Jenny Turner
106. Claire M Vajdic
107. Maria Grazia Ennas
108. Giovanni M Ferri
109. Lucia Miligi
110. Liming Liang
111. Joshua Sampson
112. Simon Crouch
113. Ju-Hyun Park
114. Kari E North
115. Angela Cox
116. John A Snowden
117. Josh Wright
118. Angel Carracedo
119. Carlos Lopez-Otin
120. Silvia Bea
121. Itziar Salaverria
122. David Martin-Garcia
123. Elias Campo
124. Joseph F Fraumeni Jr
125. Silvia de Sanjose
126. Henrik Hjalgrim
127. James R Cerhan
128. Stephen J Chanock
129. Nathaniel Rothman
130. Susan L Slager

Contributions

S.I.B., C.F.S., N.J.C., A.N., W.C., S.S.W., L.R.T., A.R.B.-W., P.H., M.P.P., B.M.B., B.K.A., P.C., Y.Z., G.S., A.Z.-J., C.L., K.E.S., J.M., P.V., J.J.S., A.K., S.d.S., H.H., J.R.C., S.J.C., N.R. and S.L.S. organized and designed the study. C.F.S., N.J.C., B.J., L.B., J.Y., A.H., L.C., P.M.B., E.A.H., J.M.C., J.R.C., S.J.C. and S.L.S. conducted and supervised the genotyping of samples. S.I.B., C.F.S., V.J., N.J.C., Z.W., N.C., C.C.C., M.Y., K.B.J., L.L., J.S., J.-H.P., J.R.C., L.C., S.J.C., N.R. and S.L.S. contributed to the design and execution of statistical analyses. S.I.B., C.F.S., V.J., N.J.C., A.N., Z.W., W.C., A.M., R.S.K., N.C., C.C.C., M.Y., C.L., H.H., J.R.C., S.J.C., N.R. and S.L.S. wrote the first draft of the manuscript. S.I.B., C.F.S., V.J., N.J.C., A.N., W.C., A.M., S.S.W., R.S.K., Q.L., L.R.T., A.R.B.-W., P.H., M.P.P., B.M.B., B.K.A., P.C., Y.Z., G.S., A.Z.-J., T.G.C., T.D.S., A.J.N., N.E.K., M.L., A.H.W., K.E.S., H.-O.A., M. Melbye, B.G., E.T.C., M.G., K.C., L.A.C.-A., B.J., W.R.D., B.K.L., G.J.W., L.C., P.M.B., J.R., E.A.H., M.T.S., R.D.J., L.F.T., S.d.S., Y.B., N.B., P. Boffetta, P. Brennan, L.F., M. Maynadie, J.M., A.S., K.G.R., S.J.A., C.M. Vachon, L.R.G., S.S.S., M.C.L., L.G.S., J.F.L., J.M.C., J.B.W., V.A.M., N.E.C., A.D.N., M.S.L., A.J.D.R., L.M.M., R.K.S., E.R., P.V., R.K., D.T., G.M., E.W., M.-D.C., R.C.H.V., R.C.T., G.G.G., D.A., J.V., S.W., J.C., T.Z., T.R.H., K.O., A.Z., R.J.K., J.J.S., K.A.B., F.L., E.G., P.K., A.K., J.T., C.M. Vajdic, M.G.E., G.M.F., L.M., L.L., J.A.S., S.C., J.F.F., K.E.N., A. Cox, J.S., J.W., A. Carracedo, C.L.-O., S.B., I.S., D.M.-G., E.C., H.H., J.R.C., N.R. and S.L.S. conducted the epidemiological studies and contributed samples to the GWAS and/or follow-up genotyping. All authors contributed to the writing of the manuscript.

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Correspondence toSusan L Slager.

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The authors declare no competing financial interests.

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Berndt, S., Skibola, C., Joseph, V. et al. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.Nat Genet 45, 868–876 (2013). https://doi.org/10.1038/ng.2652

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• Received: 16 November 2012
• Accepted: 02 May 2013
• Published: 16 June 2013
• Issue date: August 2013
• DOI: https://doi.org/10.1038/ng.2652