Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia Journal Article


Authors: Berndt, S. I.; Camp, N. J.; Skibola, C. F.; Vijai, J.; Wang, Z.; Gu, J.; Nieters, A.; Kelly, R. S.; Smedby, K. E.; Monnereau, A.; Cozen, W.; Cox, A.; Wang, S. S.; Lan, Q.; Teras, L. R.; Machado, M.; Yeager, M.; Brooks-Wilson, A. R.; Hartge, P.; Purdue, M. P.; Birmann, B. M.; Vajdic, C. M.; Cocco, P.; Zhang, Y.; Giles, G. G.; Zeleniuch-Jacquotte, A.; Lawrence, C.; Montalvan, R.; Burdett, L.; Hutchinson, A.; Ye, Y.; Call, T. G.; Shanafelt, T. D.; Novak, A. J.; Kay, N. E.; Liebow, M.; Cunningham, J. M.; Allmer, C.; Hjalgrim, H.; Adami, H. O.; Melbye, M.; Glimelius, B.; Chang, E. T.; Glenn, M.; Curtin, K.; Cannon-Albright, L. A.; Diver, W. R.; Link, B. K.; Weiner, G. J.; Conde, L.; Bracci, P. M.; Riby, J.; Arnett, D. K.; Zhi, D.; Leach, J. M.; Holly, E. A.; Jackson, R. D.; Tinker, L. F.; Benavente, Y.; Sala, N.; Casabonne, D.; Becker, N.; Boffetta, P.; Brennan, P.; Foretova, L.; Maynadie, M.; McKay, J.; Staines, A.; Chaffee, K. G.; Achenbach, S. J.; Vachon, C. M.; Goldin, L. R.; Strom, S. S.; Leis, J. F.; Weinberg, J. B.; Caporaso, N. E.; Norman, A. D.; De Roos, A. J.; Morton, L. M.; Severson, R. K.; Riboli, E.; Vineis, P.; Kaaks, R.; Masala, G.; Weiderpass, E.; Chirlaque, M. D.; Vermeulen, R. C. H.; Travis, R. C.; Southey, M. C.; Milne, R. L.; Albanes, D.; Virtamo, J.; Weinstein, S.; Clavel, J.; Zheng, T.; Holford, T. R.; Villano, D. J.; Maria, A.; Spinelli, J. J.; Gascoyne, R. D.; Connors, J. M.; Bertrand, K. A.; Giovannucci, E.; Kraft, P.; Kricker, A.; Turner, J.; Ennas, M. G.; Ferri, G. M.; Miligi, L.; Liang, L.; Ma, B.; Huang, J.; Crouch, S.; Park, J. H.; Chatterjee, N.; North, K. E.; Snowden, J. A.; Wright, J.; Fraumeni, J. F.; Offit, K.; Wu, X.; De Sanjose, S.; Cerhan, J. R.; Chanock, S. J.; Rothman, N.; Slager, S. L.
Article Title: Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Abstract: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10-8) and 3q28 (rs9815073, LPP, P=3.62 × 10-8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10-11) in the combined analysis. We find suggestive evidence (P<5 × 10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10-7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
Journal Title: Nature Communications
Volume: 7
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2016-03-09
Start Page: 10933
Language: English
DOI: 10.1038/ncomms10933
PROVIDER: scopus
PMCID: PMC4786871
PUBMED: 26956414
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    496 Offit
  2. Vijai Joseph
    113 Joseph
  3. Danylo Julian Villano
    13 Villano
  4. Ann   Maria
    7 Maria