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;Slager, Susan

2017-01-01

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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 × 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.