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

Lookup NU author(s): Dr Nicola Sunter, Dr Andrew Hall, Dr Tryfonia Mainou-Fowler, Professor Graham Jackson, Dr Helen Marr, Professor James AllanORCiD

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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 X 10 (-) (13)), 1q42.13 (rs41271473, P = 1.06 X 10 (-) (10)), 4q24 (rs71597109, P = 1.37 X 10 (-) (10)), 4q35.1 (rs57214277, P = 3.69 X 10 (-) (8)), 6p21.31 (rs3800461, P = 1.97 X 10 (-) (8)), 11q23.2 (rs61904987, P = 2.64 X 10 (-) (11)), 18q21.1 (rs1036935, P = 3.27 X 10 (-) (8)), 19p13.3 (rs7254272, P = 4.67 X 10 (-) (8)) and 22q13.33 (rs140522, P = 2.70 X 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.

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Author(s): Law PJ, Berndt SI, Speedy HE, Camp NJ, Sava GP, Skibola CF, Holroyd A, Joseph V, Sunter NJ, Nieters A, Bea S, Monnereau A, Martin-Garcia D, Goldin LR, Clot G, Teras LR, Quintela I, Birmann BM, Jayne S, Cozen W, Majid A, Smedby KE, Lan Q, Dearden C, Brooks-Wilson AR, Hall AG, Purdue MP, Mainou-Fowler T, Vajdic CM, Jackson GH, Cocco P, Marr H, Zhang YW, Zheng TZ, Giles GG, Lawrence C, Call TG, Liebow M, Melbye M, Glimelius B, Mansouri L, Glenn M, Curtin K, Diver WR, Link BK, Conde L, Bracci PM, Holly EA, Jackson RD, Tinker LF, Benavente Y, Boffetta P, Brennan P, Maynadie M, McKay J, Albanes D, Weinstein S, Wang ZM, Caporaso NE, Morton LM, Severson RK, Riboli E, Vineis P, Vermeulen RCH, Southey MC, Milne RL, Clavel J, Topka S, Spinelli JJ, Kraft P, Ennas MG, Summerfield G, Ferri GM, Harris RJ, Miligi L, Pettitt AR, North KE, Allsup DJ, Fraumeni JF, Bailey JR, Offit K, Pratt G, Hjalgrim H, Pepper C, Chanock SJ, Fegan C, Rosenquist R, de Sanjose S, Carracedo A, Dyer MJS, Catovsky D, Campo E, Cerhan JR, Allan JM, Rothman N, Houlston R, Slager SL

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2017

Volume: 8

Online publication date: 06/02/2017

Acceptance date: 06/12/2016

Date deposited: 29/03/2017

ISSN (print): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms14175

DOI: 10.1038/ncomms14175

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