Title |
Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
|
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Published in |
Nature Communications, February 2017
|
DOI | 10.1038/ncomms14175 |
Pubmed ID | |
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, 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, 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 8 | 33% |
United States | 4 | 17% |
Switzerland | 3 | 13% |
Japan | 1 | 4% |
Australia | 1 | 4% |
Malaysia | 1 | 4% |
Unknown | 6 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 14 | 58% |
Scientists | 9 | 38% |
Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Unknown | 170 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 22 | 13% |
Researcher | 22 | 13% |
Student > Master | 20 | 12% |
Student > Bachelor | 13 | 8% |
Professor | 11 | 6% |
Other | 29 | 17% |
Unknown | 54 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 39 | 23% |
Biochemistry, Genetics and Molecular Biology | 33 | 19% |
Agricultural and Biological Sciences | 12 | 7% |
Immunology and Microbiology | 4 | 2% |
Nursing and Health Professions | 3 | 2% |
Other | 17 | 10% |
Unknown | 63 | 37% |