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

Philip J Law Sonja I Berndt 1 Helen Speedy Nicola J Camp Georgina P Sava Chris Skibola Amy Holroyd 2 Vijai Joseph 3 Nicola J. Sunter Alexandra Nieters Silvia Bea Alain Monnereau David Martin-Garcia Lynn R Goldin Guillem Clot 4 Lauren R Teras Inés Quintela Brenda M Birmann Sandrine Jayne Wendy Cozen Aneela Majid 5 Karin E Smedby Qing Lan Claire Dearden Angel Brooks-Wilson Andrew G. Hall 6 Mark Purdue Tryfonia Mainou-Fowler Claire M Vajdic Graham H Jackson 7 Pierluigi Cocco Helen Marr Yawei Zhang 8 Tongzhang Zheng Graham G Giles 9 Charles Lawrence 10 Timothy G Call Mark Liebow Mads Melbye Bengt Glimelius Larry Mansouri 11 Martha Glenn 12 Karen Curtin W Ryan Diver Brian K Link 13 Lucia Conde Paige M Bracci Elizabeth A Holly Rebecca D Jackson Lesley F Tinker Yolanda Benavente Paolo Boffetta Paul Brennan Marc Maynadié 14 James Mckay Demetrius Albanes Stephanie Weinstein Zhaoming Wang Neil E Caporaso Lindsay M Morton Richard Severson Elio Riboli Paolo Vineis Roel C H Vermeulen Melissa C Southey Roger L Milne Jacqueline Clavel 15 Sabine Topka John J Spinelli Peter Kraft Maria Grazia Ennas 16 Geoffrey Summerfield Giovanni M Ferri Robert J Harris 17 Lucia Miligi Andrew R Pettitt Kari E North David J Allsup Joseph F Fraumeni James R Bailey 18 Kenneth Offit Guy Pratt 19 Henrik Hjalgrim Chris Pepper 20 Stephen J Chanock Chris Fegan Richard Rosenquist 11 Silvia de Sanjose Ángel Carracedo 21 Martin J S Dyer 22 Daniel Catovsky 23 Elias Campo James R Cerhan 24 James M Allan 25 Nathanial Rothman Richard Houlston 26, * Susan Slager 24, *
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.
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Philip J Law, Sonja I Berndt, Helen Speedy, Nicola J Camp, Georgina P Sava, et al.. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.. Nature Communications, Nature Publishing Group, 2017, 8, pp.14175. ⟨10.1038/ncomms14175⟩. ⟨hal-01545767⟩

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