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

AbstractChronic 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.