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

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 6,20...

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Detalles Bibliográficos
Autores principales: 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, 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, Slager, Susan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303820/
https://www.ncbi.nlm.nih.gov/pubmed/28165464
http://dx.doi.org/10.1038/ncomms14175
Descripción
Sumario: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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