Genome-wide association analysis implicates.pdf (953.2 kB)
Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
journal contribution
posted on 2023-06-09, 12:40 authored by Philip J Law, Sonja I Berndt, Helen E Speedy, Nicola J Camp, Georgina P Sava, Christine F Skibola, Amy Holroyd, Vijai Joseph, Nicola J Sunter, Alexandra Nieters, Silvia Bea, Alain Monnereau, David Martin-Garcia, 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 R. Brooks-Wilson, Andrew G Hall, Mark P Purdue, Tryfonia Mainou-Fowler, Claire M Vajdic, Graham H 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, Lucia 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 Weinstein, Zhaoming Wang, Neil E. Caporaso, Lindsay M Morton, Richard K Severson, Elio Riboli, Paolo Vineis, Roel C H Vermeulen, Melissa C Southey, Roger L. Milne, Jacqueline Clavel, Sabine Topka, John J Spinelli, Peter Kraft, Maria Grazia Ennas, Geoffrey Summerfield, Giovanni M Ferri, Robert J Harris, Lucia Miligi, Andrew R Pettitt, Kari E North, David J Allsup, Joseph F Fraumeni, James R Bailey, Kenneth Offit, Guy Pratt, Henrik Hjalgrim, Christopher PepperChristopher Pepper, Stephen J Chanock, Chris Fegan, Richard Rosenquist, Silvia de Sanjose, Angel Carracedo, Martin J S Dyer, Daniel Catovsky, Elias Campo, James R. Cerhan, James M Allan, Nathanial Rothman, Richard Houlston, Susan SlagerSeveral 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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Publication status
- Published
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- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature Publishing GroupExternal DOI
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8Page range
1-12Department affiliated with
- Clinical and Experimental Medicine Publications
Research groups affiliated with
- Haematology Research Group Publications
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- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-03-28First Open Access (FOA) Date
2018-03-28First Compliant Deposit (FCD) Date
2018-03-28Usage metrics
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