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 and Slager, Susan (2017) Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. Nature communications, 8. p. 14175. ISSN 2041-1723. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

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Official URL: http://www.nature.com/articles/ncomms14175

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.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
Depositing User: Mrs Caroline Tranter
Date Deposited: 31 Mar 2017 11:10
Last Modified: 31 Mar 2017 11:10
URI: http://www.repository.uhblibrary.co.uk/id/eprint/1334

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