A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1.
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Date
2017-03-01Author
Vijayakrishnan, J
Kumar, R
Henrion, MYR
Moorman, AV
Rachakonda, PS
Hosen, I
da Silva Filho, MI
Holroyd, A
Dobbins, SE
Koehler, R
Thomsen, H
Irving, JA
Allan, JM
Lightfoot, T
Roman, E
Kinsey, SE
Sheridan, E
Thompson, PD
Hoffmann, P
Nöthen, MM
Heilmann-Heimbach, S
Jöckel, KH
Greaves, M
Harrison, CJ
Bartram, CR
Schrappe, M
Stanulla, M
Hemminki, K
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10-9). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology.
Collections
Subject
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 12
Humans
Chromosome Deletion
Genetic Predisposition to Disease
Case-Control Studies
Gene Expression Profiling
Sequence Analysis, DNA
Computational Biology
Chromatin Assembly and Disassembly
Genotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Child
Child, Preschool
Infant
Female
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genome-Wide Association Study
Genetic Loci
Molecular Sequence Annotation
High-Throughput Nucleotide Sequencing
Research team
Cancer Genomics
Biology of Childhood Leukaemia
Language
eng
Date accepted
2016-09-06
License start date
2017-03
Citation
Leukemia, 2017, 31 (3), pp. 573 - 579
Publisher
NATURE PUBLISHING GROUP