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 FORETOVÁ 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. ROOS Anneclaire J De 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 SANJOSE Silvia de CERHAN James R. CHANOCK Stephen J. ROTHMAN Nathaniel SLAGER Susan L.
Year of publication	2016
Type	Article in Periodical
Magazine / Source	Nature Communications
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1038/ncomms10933
Field	Oncology and hematology
Keywords	TRANSCRIPTION FACTOR EOMESODERMIN; FAS GENE-MUTATIONS; SUSCEPTIBILITY LOCI; FOLLICULAR LYMPHOMA; RISK; VARIANTS; EXPRESSION; BANK1; PRIORITIZATION; CLASSIFICATION
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 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 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.