Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.
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Law, Philip J | Berndt, Sonja I | Speedy, Helen | Camp, Nicola J | Sava, Georgina P | Skibola, Chris | 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, Angel | Hall, Andrew G. | Purdue, Mark | 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 | Maynadié, Marc | Mckay, James | Albanes, Demetrius | Weinstein, Stephanie | Wang, Zhaoming | Caporaso, Neil E | Morton, Lindsay M | Severson, Richard | 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, Ángel | Dyer, Martin J S | Catovsky, Daniel | Campo, Elias | Cerhan, James R | Allan, James M | Rothman, Nathanial | Houlston, Richard | Slager, Susan
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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.
