Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk.
MetadataShow full item record
There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10<sup>-8</sup>), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10<sup>-8</sup>) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10<sup>-8</sup>), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10<sup>-8</sup>). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL.
Version of record
Genetic Predisposition to Disease
Oncogene Proteins, Fusion
Polymorphism, Single Nucleotide
Core Binding Factor Alpha 2 Subunit
bcl-2 Homologous Antagonist-Killer Protein
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Genome-Wide Association Study
License start date
Nature communications, 2019, 10 (1), pp. 5348 - ?