A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1.

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ICR Authors

Vijayakrishnan, Jayaram
 Holroyd, Amy
 Greaves, Melvyn
 Houlston, Richard

Authors

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

Document Type

Journal Article

Date

2017-03-01

Date Accepted

2016-09-06

Abstract

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.

Citation

Leukemia, 2017, 31 (3), pp. 573 - 579

DOI

10.1038/leu.2016.271

URI

https://repository.icr.ac.uk/handle/internal/308

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

NATURE PUBLISHING GROUP

ISSN

0887-6924

eISSN

1476-5551

Collections

Cancer Biology
Genetics and Epidemiology

Research Team

Cancer Genomics
Biology of Childhood Leukaemia

Notes