Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a tota...

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Detalles Bibliográficos
Autores: Berndt, Sonja I., Skibola, Christine F., Joseph, Vijai, Camp, Nicola J., Nieters, Alexandra, Wang, Zhaoming, Cozen, Wendy, Monnereau, Alain, Wang, Sophia S., Kelly, Rachel S., Lan, Qing, Teras, Lauren R., Chatterjee, Nilanjan, Chung, Charles C., Yeager, Meredith, Brooks-Wilson, Angela R., Hartge, Patricia, Purdue, Mark P., Birmann, Brenda M., Armstrong, Bruce K., Cocco, Pierluigi, Zhang, Yawei, Severi, Gianluca, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Burdette, Laurie, Yuenger, Jeffrey, Hutchinson, Amy, Jacobs, Kevin B., Call, Timothy G., Shanafelt, Tait D., Novak, Anne J., Kay, Neil E., Liebow, Mark, Wang, Alice H., Smedby, Karin E., Adami, Hans-Olov, Melbye, Mads, Glimelius, Bengt, Chang, Ellen T., Glenn, Martha, Curtin, Karen, Cannon-Albright, Lisa A., Jones, Brandt, Diver, W. Ryan, Link, Brian K., Weiner, George J., Conde, Lucía, Bracci, Paige M., Riby, Jacques, Holly, Elizabeth A., Smith, Martyn T., Jackson, Rebecca D. J., Tinker, Lesley F., Benavente, Yolanda, Becker, Nikolaus, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadié, Marc, McKay, James D., Staines, Anthony
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126022
Acceso en línea:https://hdl.handle.net/2445/126022
Access Level:acceso abierto
Palabra clave:Leucèmia limfocítica crònica
Genòmica
Chronic lymphocytic leukemia
Genomics
Descripción
Sumario:Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

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