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


Authors: Berndt, S. I.; Skibola, C. F.; Joseph, V.; Camp, N. J.; Nieters, A.; Wang, Z.; Cozen, W.; Monnereau, A.; Wang, S. S.; Kelly, R. S.; Lan, Q.; Teras, L. R.; Chatterjee, N.; Chung, C. C.; Yeager, M.; Brooks-Wilson, A. R.; Hartge, P.; Purdue, M. P.; Birmann, B. M.; Armstrong, B. K.; Cocco, P.; Zhang, Y.; Severi, G.; Zeleniuch-Jacquotte, A.; Lawrence, C.; Burdette, L.; Yuenger, J.; Hutchinson, A.; Jacobs, K. B.; Call, T. G.; Shanafelt, T. D.; Novak, A. J.; Kay, N. E.; Liebow, M.; Wang, A. H.; Smedby, K. E.; Adami, H. O.; Melbye, M.; Glimelius, B.; Chang, E. T.; Glenn, M.; Curtin, K.; Cannon-Albright, L. A.; Jones, B.; Diver, W. R.; Link, B. K.; Weiner, G. J.; Conde, L.; Bracci, P. M.; Riby, J.; Holly, E. A.; Smith, M. T.; Jackson, R. D.; Tinker, L. F.; Benavente, Y.; Becker, N.; Boffetta, P.; Brennan, P.; Foretova, L.; Maynadie, M.; McKay, J.; Staines, A.; Rabe, K. G.; Achenbach, S. J.; Vachon, C. M.; Goldin, L. R.; Strom, S. S.; Lanasa, M. C.; Spector, L. G.; Leis, J. F.; Cunningham, J. M.; Weinberg, J. B.; Morrison, V. A.; Caporaso, N. E.; Norman, A. D.; Linet, M. S.; De Roos, A. J.; Morton, L. M.; Severson, R. K.; Riboli, E.; Vineis, P.; Kaaks, R.; Trichopoulos, D.; Masala, G.; Weiderpass, E.; Chirlaque, M. D.; Vermeulen, R. C. H.; Travis, R. C.; Giles, G. G.; Albanes, D.; Virtamo, J.; Weinstein, S.; Clavel, J.; Zheng, T.; Holford, T. R.; Offit, K.; Zelenetz, A.; Klein, R. J.; Spinelli, J. J.; Bertrand, K. A.; Laden, F.; Giovannucci, E.; Kraft, P.; Kricker, A.; Turner, J.; Vajdic, C. M.; Grazia Ennas, M.; Ferri, G. M.; Miligi, L.; Liang, L.; Sampson, J.; Crouch, S.; Park, J. H.; North, K. E.; Cox, A.; Snowden, J. A.; Wright, J.; Carracedo, A.; Lopez-Otin, C.; Bea, S.; Salaverria, I.; Martin-Garcia, D.; Campo, E.; Fraumeni, J. F. Jr; de Sanjose, S.; Hjalgrim, H.; Cerhan, J. R.; Chanock, S. J.; Rothman, N.; Slager, S. L.
Article Title: Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
Abstract: 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 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 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. © 2013 Nature America, Inc. All rights reserved.
Keywords: signal transduction; protein expression; unclassified drug; gene mutation; single nucleotide polymorphism; protein bcl 2; apoptosis; protein; gene locus; genetic association; genotype; acute lymphoblastic leukemia; hodgkin disease; genetic susceptibility; telomerase reverse transcriptase; autoimmunity; caspase 8; genetic risk; chronic lymphatic leukemia; mitochondrial protein; wnt protein; caspase 10; meta analysis; lymphoid enhancer factor 1; cyclin dependent kinase inhibitor 2b; gene linkage disequilibrium; protein acta 2; protein bcl2l 11; protein pmaip 1; protein prkd 3; monoclonal b cell lymphocytosis
Journal Title: Nature Genetics
Volume: 45
Issue: 8
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2013-08-01
Start Page: 868
End Page: 876
Language: English
DOI: 10.1038/ng.2652
PROVIDER: scopus
PMCID: PMC3729927
PUBMED: 23770605
DOI/URL:
Notes: --- - "Export Date: 4 September 2013" - "CODEN: NGENE" - "Source: Scopus"
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  1. Kenneth Offit
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  2. Andrew D Zelenetz
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  3. Robert J. Klein
    60 Klein
  4. Vijai Joseph
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