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

J Vijayakrishnan; R Kumar; M Y R Henrion; A V Moorman; P S Rachakonda; I Hosen; M I de Silva Filho; A Holroyd; S E Dobbins; R Koehler; H Thomsen; J A Irving; J M Allen; Tracy Jayne Lightfoot; Eve 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, M Y R Henrion, A V Moorman, P S Rachakonda, I Hosen, M I de Silva Filho, A Holroyd, S E Dobbins, R Koehler, H Thomsen, J A Irving, J M Allen, Tracy Jayne Lightfoot, Eve Roman, S.E. Kinsey, E Sheridan, P D Thompson, P Hoffmann, M M NöthenS Heilmann-Heimbach, K H Jöckel, M. Greaves, C J Harrison, C R Bartram, M Schrappe, M Stanulla, K Hemminki, R S Houlston

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

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
Early online date	11 Nov 2016
DOIs	https://doi.org/10.1038/leu.2016.271
Publication status	Published - 2017

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Cite this

Vijayakrishnan, J., Kumar, R., Henrion, M. Y. R., Moorman, A. V., Rachakonda, P. S., Hosen, I., de Silva Filho, M. I., Holroyd, A., Dobbins, S. E., Koehler, R., Thomsen, H., Irving, J. A., Allen, J. M., Lightfoot, T. J., 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{79c68047334d4ece954f7d2b719cdf76,

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 ofchildhood 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 susceptibilityloci 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 alsoprovide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked byrs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Ourdata provide further insights into genetic susceptibility to ALL and its biology",

author = "J Vijayakrishnan and R Kumar and Henrion, {M Y R} and Moorman, {A V} and Rachakonda, {P S} and I Hosen and {de Silva Filho}, {M I} and A Holroyd and Dobbins, {S E} and R Koehler and H Thomsen and Irving, {J A} and Allen, {J M} and Lightfoot, {Tracy Jayne} and Eve Roman and S.E. Kinsey 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}",

note = "{\textcopyright} The Author(s) 2017",

year = "2017",

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, MYR, Moorman, AV, Rachakonda, PS, Hosen, I, de Silva Filho, MI, Holroyd, A, Dobbins, SE, Koehler, R, Thomsen, H, Irving, JA, Allen, JM, Lightfoot, TJ , 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, M Y R

AU - Moorman, A V

AU - Rachakonda, P S

AU - Hosen, I

AU - de Silva Filho, M I

AU - Holroyd, A

AU - Dobbins, S E

AU - Koehler, R

AU - Thomsen, H

AU - Irving, J A

AU - Allen, J M

AU - Lightfoot, Tracy Jayne

AU - Roman, Eve

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

Y1 - 2017

N2 - Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk ofchildhood 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 susceptibilityloci 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 alsoprovide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked byrs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Ourdata 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 ofchildhood 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 susceptibilityloci 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 alsoprovide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked byrs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Ourdata 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 -