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

Law, Philip J and Berndt, Sonja I and Speedy, Helen E and Camp, Nicola J and Sava, Georgina P and Skibola, Christine F and Holroyd, Amy and Joseph, Vijai and Sunter, Nicola J and Nieters, Alexandra and Bea, Silvia and Monnereau, Alain and Martin-Garcia, David and Goldin, Lynn R and Clot, Guillem and Teras, Lauren R and Quintela, Inés and Birmann, Brenda M and Jayne, Sandrine and Cozen, Wendy and Majid, Aneela and Smedby, Karin E and Lan, Qing and Dearden, Claire and Brooks-Wilson, Angela R and Hall, Andrew G and Purdue, Mark P and Mainou-Fowler, Tryfonia and Vajdic, Claire M and Jackson, Graham H and Cocco, Pierluigi and Marr, Helen and Zhang, Yawei and Zheng, Tongzhang and Giles, Graham G and Lawrence, Charles and Call, Timothy G and Liebow, Mark and Melbye, Mads and Glimelius, Bengt and Mansouri, Larry and Glenn, Martha and Curtin, Karen and Diver, W Ryan and Link, Brian K and Conde, Lucia and Bracci, Paige M and Holly, Elizabeth A and Jackson, Rebecca D and Tinker, Lesley F and Benavente, Yolanda and Boffetta, Paolo and Brennan, Paul and Maynadie, Marc and McKay, James and Albanes, Demetrius and Weinstein, Stephanie and Wang, Zhaoming and Caporaso, Neil E and Morton, Lindsay M and Severson, Richard K and Riboli, Elio and Vineis, Paolo and Vermeulen, Roel C H and Southey, Melissa C and Milne, Roger L and Clavel, Jacqueline and Topka, Sabine and Spinelli, John J and Kraft, Peter and Ennas, Maria Grazia and Summerfield, Geoffrey and Ferri, Giovanni M and Harris, Robert J and Miligi, Lucia and Pettitt, Andrew R and North, Kari E and Allsup, David J and Fraumeni, Joseph F and Bailey, James R and Offit, Kenneth and Pratt, Guy and Hjalgrim, Henrik and Pepper, Chris and Chanock, Stephen J and Fegan, Chris and Rosenquist, Richard and de Sanjose, Silvia and Carracedo, Angel and Dyer, Martin J S and Catovsky, Daniel and Campo, Elias and Cerhan, James R and Allan, James M and Rothman, Nathanial and 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.heartofengland.nhs.uk/id/eprint/1334

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