Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.
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, SI; Camp, NJ; Skibola, CF; Vijai, J; Wang, Z; Gu, J; Nieters, A; Kelly, RS; Smedby, KE; Monnereau, A; Cozen, W; Cox, A; Wang, SS; Lan, Q; Teras, LR; Machado, M; Yeager, M; Brooks-Wilson, AR; Hartge, P; Purdue, MP; Birmann, BM; Vajdic, CM; Cocco, P; Zhang, Y; Giles, GG; Zeleniuch-Jacquotte, A; Lawrence, C; Montalvan, R; Burdett, L; Hutchinson, A; Ye, Y; Call, TG; Shanafelt, TD; Novak, AJ; Kay, NE; Liebow, M; Cunningham, JM; Allmer, C; Hjalgrim, H; Adami, H-O; Melbye, M; Glimelius, B; Chang, ET; Glenn, M; Curtin, K; Cannon-Albright, LA; Diver, WR; Link, BK; Weiner, GJ; Conde, L; Bracci, PM; Riby, J; Arnett, DK; Zhi, D; Leach, JM; Holly, EA; Jackson, RD; Tinker, LF; Benavente, Y; Sala, N; Casabonne, D; Becker, N; Boffetta, P; Brennan, P; Foretova, L; Maynadie, M; McKay, J; Staines, A; Chaffee, KG; Achenbach, SJ; Vachon, CM; Goldin, LR; Strom, SS; Leis, JF; Weinberg, JB; Caporaso, NE; Norman, AD; De Roos, AJ; Morton, LM; Severson, RK; Riboli, E; Vineis, P; Kaaks, R; Masala, G; Weiderpass, E; Chirlaque, M-D; Vermeulen, RCH; Travis, RC; Southey, MC; Milne, RL; Albanes, D; Virtamo, J; Weinstein, S; Clavel, J; Zheng, T; Holford, TR; Villano, DJ; Maria, A; Spinelli, JJ; Gascoyne, RD; Connors, JM; Bertrand, KA; Giovannucci, E; Kraft, P; Kricker, A; Turner, J; Ennas, MG; Ferri, GM; Miligi, L; Liang, L; Ma, B; Huang, J; Crouch, S; Park, J-H; Chatterjee, N; North, KE; Snowden, JA; Wright, J; Fraumeni, JF; Offit, K; Wu, X; de Sanjose, S; Cerhan, JR; Chanock, SJ; Rothman, N; Slager, SL
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