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

description: 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.