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

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.

doi:10.1038/ncomms10933

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.

Berndt, S., Camp, N., Skibola, C., Vijai, J., Wang, Z., Gu, J., et al. (2016). Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. NATURE COMMUNICATIONS, 7, 1-9 [10.1038/ncomms10933].