title: 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
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authors.initials: J
authors.lastname: Wright
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.affiliation: Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.|CIBER de Epidemiología y Salud Pública (CIBERESP), 08036 Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjose
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015843:Serpins / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C447641:BANK1 protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C434543:CSRNP1 protein, human; C491199:EOMES protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D015843:Serpins; D020825:T-Box Domain Proteins; C094472:serpin B6