Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
Berndt, Sonja-I; Lan, Qing; Hartge, Patricia; Goldin, Lynn-R; Caporaso, Neil-E; Morton, Lindsay-M; Albanese, Demetrius; Weinstein, Stephanie; Chatterjee, Nilanjan; Fraumeni, Joseph-F; Chanock, Stephen-J; Rothman, Nathaniel; Camp, Nicola-J; Arnett, Donna-K; Skibola, Christine-F; Conde, Lucia; Riby, Jacques; Vijai, Joseph; Villano, Danylo-J; Maria, Ann; Offit, Kenneth; Wang, Zhaoming; Yeager, Meredith; Burdett, Laurie; Hutchinson, Amy; Gu, Jian; Ye, Yuanqing; Strom, Sara-S; Wu, Xifeng; Nieters, Alexandra; Huang, Jinyan; Kelly, Rachel-S; Smedby, Karin-E; Clavel, Jacqueline; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia-S; Teras, Lauren-R; Diver, W-Ryan; Machado, Moara; Brooks-Wilson, Angela-R; Purdue, Mark-P; Birmann, Brenda-M; Bertrand, Kimberly-A; Vajdic, Claire-M; Cocco, Pierluigi; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham-G; Milne, Roger-L; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Call, Timothy-G; Kay, Neil-E; Shanafelt, Tait-D; Novak, Anne-J; Liebow, Mark; Cunningham, Julie-M; Allmer, Cristine; Chaffee, Kari-G; Achenbach, Sara-J; Vachon, Celine-M; Norman, Aaron-D; Cerhan, James-R; Slager, Susan-L; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen-T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa-A; Link, Brian-K; Weiner, George-J; Bracci, Paige-M; Holly, Elizabeth-A; Zhi, Degui; Leach, Justin-M; Jackson, Rebecca-D; Tinker, Lesley-F; Benavente, Yolanda; de-Sanjose, Silvia; Sala, Nuria; Casabonne, Delphine; Becker, Nikolaus; Kaaks, Rudolph; Boffetta, Paolo; Brennan, Paul; McKay, James; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Leis, José-F; Weinberg, J-Brice; De-Roos, Anneclaire-J; Severson, Richard-K; Riboli, Elio; Vineis, Paolo; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque-López, María-Dolores; Vermeulen, Roel-C-H; Travis, Ruth-C; Southey, Melissa-C; Virtamo, Jarmo; Holford, Theodore-R; Spinelli, John-J; Gascoyne, Randy-D; Connors, Joseph-M; Giovannucci, Edward; Kraft, Peter; Liang, Liming; Kricker, Anne; Turner, Jenny; Ennas, María-Grazia; Ferri, Giovanni-M; Miligi, Lucia; Ma, Baoshan; Crouch, Simon; Park, Ju-Hyun; North, Kari-E; Snowden, John-A; Wright, Josh
Fecha:
2016-03-09
Resumen:
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.
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