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

Lookup NU author(s): Professor Anthony MoormanORCiD, Professor Julie Irving, Professor James Allan, Professor Christine Harrison FRCPath FMedSci

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Abstract

© 2017 The Author(s). 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.

Publication metadata

Author(s): 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, Jockel KH, Greaves M, Harrison CJ, Bartram CR, Schrappe M, Stanulla M, Hemminki K, Houlston RS

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2017

Volume: 31

Issue: 3

Pages: 573-579

Print publication date: 01/03/2017

Online publication date: 11/11/2016

Acceptance date: 06/09/2016

Date deposited: 10/04/2017

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/leu.2016.271

DOI: 10.1038/leu.2016.271

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