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

2017; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/ncomms14175

2041-1723

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

Immunodeficiency and Autoimmune Disorders

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.