Journal Article

Meta-Analysis

Research Support, N.I.H., Extramural

Research Support, N.I.H., Intramural

Research Support, Non-U.S. Gov't

Research Support, U.S. Gov't, Non-P.H.S.

Research Support, U.S. Gov't, P.H.S.

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

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

Nature Communications 2016 March 10

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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