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

J. Vijayakrishnan; R. Kumar; Marc Henrion; A. V. Moorman; P. S. Rachakonda; I. Hosen; M. I. Da Silva Filho; A. Holroyd; S. E. Dobbins; R. Koehler; H. Thomsen; J. A. Irving; J. M. Allan; T. Lightfoot; E. Roman; S. E. Kinsey; E. Sheridan; P. D. Thompson; P. Hoffmann; M. M. Nöthen; S. Heilmann-Heimbach; K. H. Jöckel; M. Greaves; C. J. Harrison; C. R. Bartram; M. Schrappe; M. Stanulla; K. Hemminki; R. S. Houlston

doi:10.1038/leu.2016.271

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

J. Vijayakrishnan
, R. Kumar
, Marc Henrion
, A. V. Moorman
, P. S. Rachakonda
, I. Hosen
, M. I. Da Silva Filho
, A. Holroyd
, S. E. Dobbins
, R. Koehler
, H. Thomsen
, J. A. Irving
, J. M. Allan
, T. Lightfoot
, E. Roman
, S. E. Kinsey
, E. Sheridan
, P. D. Thompson
, P. Hoffmann
, M. M. Nöthen

S. Heilmann-Heimbach, K. H. Jöckel, M. Greaves, C. J. Harrison, C. R. Bartram, M. Schrappe, M. Stanulla, K. Hemminki, R. S. Houlston

Institute of Cancer Research
German Cancer Research Center
Newcastle University
Heidelberg University
University of York
Leeds General Infirmary
University of Leeds
University of Manchester
University of Bonn
University of Basel
University of Duisburg-Essen
University Hospital Schleswig-Holstein
Hannover Medical School
Lund University

Research output: Contribution to journal › Article › peer-review

76 Citations (Scopus)

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.

Original language	English
Pages (from-to)	573-579
Number of pages	7
Journal	Leukemia
Volume	31
Issue number	3
DOIs	https://doi.org/10.1038/leu.2016.271
Publication status	Published - 1 Mar 2017
Externally published	Yes

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SDG 3 Good Health and Well-being

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Vijayakrishnan, J., Kumar, R., Henrion, M., Moorman, A. V., Rachakonda, P. S., Hosen, I., Da Silva Filho, M. I., Holroyd, A., Dobbins, S. E., Koehler, R., Thomsen, H., Irving, J. A., Allan, J. M., Lightfoot, T., Roman, E., Kinsey, S. E., Sheridan, E., Thompson, P. D., Hoffmann, P., ... Houlston, R. S. (2017). A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1. Leukemia, 31(3), 573-579. https://doi.org/10.1038/leu.2016.271

@article{43e51ebfcb0c4a0e86e7bde2bd2482e9,

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

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.",

author = "J. Vijayakrishnan and R. Kumar and Marc Henrion and Moorman, \{A. V.\} and Rachakonda, \{P. S.\} and I. Hosen and \{Da Silva Filho\}, \{M. I.\} and A. Holroyd and Dobbins, \{S. E.\} and R. Koehler and H. Thomsen and Irving, \{J. A.\} and Allan, \{J. M.\} and T. Lightfoot and E. Roman and Kinsey, \{S. E.\} and E. Sheridan and Thompson, \{P. D.\} and P. Hoffmann and N{\"o}then, \{M. M.\} and S. Heilmann-Heimbach and J{\"o}ckel, \{K. H.\} and M. Greaves and Harrison, \{C. J.\} and Bartram, \{C. R.\} and M. Schrappe and M. Stanulla and K. Hemminki and Houlston, \{R. S.\}",

year = "2017",

month = mar,

day = "1",

doi = "10.1038/leu.2016.271",

language = "English",

volume = "31",

pages = "573--579",

journal = "Leukemia",

issn = "0887-6924",

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Vijayakrishnan, J, Kumar, R, Henrion, M, 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 2017, 'A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1', Leukemia, vol. 31, no. 3, pp. 573-579. https://doi.org/10.1038/leu.2016.271

TY - JOUR

T1 - A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1

AU - Vijayakrishnan, J.

AU - Kumar, R.

AU - Henrion, Marc

AU - Moorman, A. V.

AU - Rachakonda, P. S.

AU - Hosen, I.

AU - Da Silva Filho, M. I.

AU - Holroyd, A.

AU - Dobbins, S. E.

AU - Koehler, R.

AU - Thomsen, H.

AU - Irving, J. A.

AU - Allan, J. M.

AU - Lightfoot, T.

AU - Roman, E.

AU - Kinsey, S. E.

AU - Sheridan, E.

AU - Thompson, P. D.

AU - Hoffmann, P.

AU - Nöthen, M. M.

AU - Heilmann-Heimbach, S.

AU - Jöckel, K. H.

AU - Greaves, M.

AU - Harrison, C. J.

AU - Bartram, C. R.

AU - Schrappe, M.

AU - Stanulla, M.

AU - Hemminki, K.

AU - Houlston, R. S.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

U2 - 10.1038/leu.2016.271

DO - 10.1038/leu.2016.271

M3 - Article

SN - 0887-6924

VL - 31

SP - 573

EP - 579

JO - Leukemia

JF - Leukemia

IS - 3

ER -

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

Abstract

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