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

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 ORCID: https://orcid.org/0000-0001-9685-0621, 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 and Slager, Susan 2017. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. Nature Communications 8 , 14175. 10.1038/ncomms14175

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Uncontrolled Keywords:	B-cell lymphoma; Cancer epidemiology; Genome-wide association studies
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	13 December 2017
Date of Acceptance:	6 December 2016
Last Modified:	22 May 2023 18:37
URI:	https://orca.cardiff.ac.uk/id/eprint/102635

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