Berndt, SI;Camp, NJ;Skibola, CF;Vijai, J;Wang, ZM;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, YW;Giles, GG;Zeleniuch-Jacquotte, A;Lawrence, C;Montalvan, R;Burdett, L;Hutchinson, A;Ye, YQ;Call, TG;Shanafelt, TD;Novak, AJ;Kay, NE;Liebow, M;Cunningham, JM;Allmer, C;Hjalgrim, H;Adami, HO;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, DG;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, MD;Vermeulen, RCH;Travis, RC;Southey, MC;Milne, RL;Albanese, D;Virtamo, J;Weinstein, S;Clavel, J;Zheng, TZ;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, LM;Ma, BS;Huang, JY;Crouch, S;Park, JH;Chatterjee, N;North, KE;Snowden, JA;Wright, J;Fraumeni, JF;Offit, K;Wu, XF;de Sanjose, S;Cerhan, JR;Chanock, SJ;Rothman, N;Slager, SL

2016

March

Nature Communications

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

Published

41 ()

TRANSCRIPTION FACTOR EOMESODERMIN FAS GENE-MUTATIONS SUSCEPTIBILITY LOCI FOLLICULAR LYMPHOMA RISK VARIANTS EXPRESSION BANK1 PRIORITIZATION CLASSIFICATION

7

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 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 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.

LONDON

2041-1723

10.1038/ncomms10933