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

Abstract

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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Item Type:	Article
Authors/Creators:	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 https://orcid.org/0000-0002-3026-2859 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
Copyright, Publisher and Additional Information:	This content is made available by the publisher under a Creative Commons Attribution Licence. This means that a user may copy, distribute and display the resource providing that they give credit. Users must adhere to the terms of the licence.
Dates:	Published: 9 March 2016 Accepted: 3 February 2016
Institution:	The University of York
Academic Units:	The University of York > Faculty of Sciences (York) > Health Sciences (York)
Depositing User:	Pure (York)
Date Deposited:	11 Mar 2016 11:19
Last Modified:	16 Oct 2024 12:52
Published Version:	https://doi.org/10.1038/ncomms10933
Status:	Published
Refereed:	Yes
Identification Number:	10.1038/ncomms10933
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:96335

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

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