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

Publication Type:

Journal Article

Authors:

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

Source:

Nature communications, Volume 8, p.14175 (2017)

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.