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=2.55x10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97x10-8), and 3q28 (rs9815073, LPP, P=3.62x10-8) as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00x10-11) in the combined analysis. We find suggestive evidence (P<5x10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19x10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12x10-7). 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.

Meta-analysis of Genome-wide Association Studies Discovers Multiple Loci for Chronic Lymphocytic Leukemia.

FERRI, Giovanni Maria;
2016-01-01

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=2.55x10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97x10-8), and 3q28 (rs9815073, LPP, P=3.62x10-8) as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00x10-11) in the combined analysis. We find suggestive evidence (P<5x10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19x10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12x10-7). 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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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/147467
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