Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia

Jayaram Vijayakrishnan; James Studd; Peter Broderick; Ben Kinnersley; Amy Holroyd; Philip J. Law; Rajiv Kumar; James M. Allan; Christine J. Harrison; Anthony V. Moorman; Ajay Vora; Eve Roman; Sivaramakrishna Rachakonda; Sally E. Kinsey; Eamonn Sheridan; Pamela D. Thompson; Julie A. Irving; Rolf Koehler; Per Hoffmann; Markus M. Nöthen; Stefanie Heilmann-Heimbach; Karl Heinz Jöckel; Douglas F. Easton; Paul D.P. Pharaoh; Alison M. Dunning; Julian Peto; Frederico Canzian; Anthony Swerdlow; Rosalind A. Eeles; ZSofia Kote-Jarai; Kenneth Muir; Nora Pashayan; Mel Greaves; Martin Zimmerman; Claus R. Bartram; Martin Schrappe; Martin Stanulla; Kari Hemminki; Richard S. Houlston; Brian E. Henderson; Christopher A. Haiman; Sara Benlloch; Fredrick R. Schumacher; Ali Amin Al Olama; Sonja I. Berndt; David V. Conti; Fredrik Wiklund; Stephen Chanock; Victoria L. Stevens; Børge G. Nordestgaard; The Practical Consortium

doi:10.1038/s41467-018-03178-z

Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia

Jayaram Vijayakrishnan, James Studd, Peter Broderick, Ben Kinnersley, Amy Holroyd, Philip J. Law, Rajiv Kumar, James M. Allan, Christine J. Harrison, Anthony V. Moorman, Ajay Vora, Eve Roman, Sivaramakrishna Rachakonda, Sally E. Kinsey, Eamonn Sheridan, Pamela D. Thompson, Julie A. Irving, Rolf Koehler, Per Hoffmann, Markus M. NöthenStefanie Heilmann-Heimbach, Karl Heinz Jöckel, Douglas F. Easton, Paul D.P. Pharaoh, Alison M. Dunning, Julian Peto, Frederico Canzian, Anthony Swerdlow, Rosalind A. Eeles, ZSofia Kote-Jarai, Kenneth Muir, Nora Pashayan, Mel Greaves, Martin Zimmerman, Claus R. Bartram, Martin Schrappe, Martin Stanulla, Kari Hemminki, Richard S. Houlston^*, Brian E. Henderson, Christopher A. Haiman, Sara Benlloch, Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen Chanock, Victoria L. Stevens, Børge G. Nordestgaard, The Practical Consortium

^*Corresponding author for this work

Department of Clinical Medicine

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Abstract

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10^-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10^-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.

Original language	English
Article number	1340
Journal	Nature Communications
Volume	9
Issue number	1
Number of pages	14
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-03178-z
Publication status	Published - 2018

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Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemiaFinal published version, 915 KBLicence: CC BY

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Vijayakrishnan, J., Studd, J., Broderick, P., Kinnersley, B., Holroyd, A., Law, P. J., Kumar, R., Allan, J. M., Harrison, C. J., Moorman, A. V., Vora, A., Roman, E., Rachakonda, S., Kinsey, S. E., Sheridan, E., Thompson, P. D., Irving, J. A., Koehler, R., Hoffmann, P., ... The Practical Consortium (2018). Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia. Nature Communications, 9(1), [1340]. https://doi.org/10.1038/s41467-018-03178-z

Vijayakrishnan, J, Studd, J, Broderick, P, Kinnersley, B, Holroyd, A, Law, PJ, Kumar, R, Allan, JM, Harrison, CJ, Moorman, AV, Vora, A, Roman, E, Rachakonda, S, Kinsey, SE, Sheridan, E, Thompson, PD, Irving, JA, Koehler, R, Hoffmann, P, Nöthen, MM, Heilmann-Heimbach, S, Jöckel, KH, Easton, DF, Pharaoh, PDP, Dunning, AM, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, ZS, Muir, K, Pashayan, N, Greaves, M, Zimmerman, M, Bartram, CR, Schrappe, M, Stanulla, M, Hemminki, K, Houlston, RS, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Olama, AAA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Nordestgaard, BG & The Practical Consortium 2018, 'Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia', Nature Communications, vol. 9, no. 1, 1340. https://doi.org/10.1038/s41467-018-03178-z

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title = "Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia",

abstract = "Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.",

author = "Jayaram Vijayakrishnan and James Studd and Peter Broderick and Ben Kinnersley and Amy Holroyd and Law, {Philip J.} and Rajiv Kumar and Allan, {James M.} and Harrison, {Christine J.} and Moorman, {Anthony V.} and Ajay Vora and Eve Roman and Sivaramakrishna Rachakonda and Kinsey, {Sally E.} and Eamonn Sheridan and Thompson, {Pamela D.} and Irving, {Julie A.} and Rolf Koehler and Per Hoffmann and N{\"o}then, {Markus M.} and Stefanie Heilmann-Heimbach and J{\"o}ckel, {Karl Heinz} and Easton, {Douglas F.} and Pharaoh, {Paul D.P.} and Dunning, {Alison M.} and Julian Peto and Frederico Canzian and Anthony Swerdlow and Eeles, {Rosalind A.} and ZSofia Kote-Jarai and Kenneth Muir and Nora Pashayan and Mel Greaves and Martin Zimmerman and Bartram, {Claus R.} and Martin Schrappe and Martin Stanulla and Kari Hemminki and Houlston, {Richard S.} and Henderson, {Brian E.} and Haiman, {Christopher A.} and Sara Benlloch and Schumacher, {Fredrick R.} and Olama, {Ali Amin Al} and Berndt, {Sonja I.} and Conti, {David V.} and Fredrik Wiklund and Stephen Chanock and Stevens, {Victoria L.} and Nordestgaard, {B{\o}rge G.} and {The Practical Consortium}",

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AU - Vijayakrishnan, Jayaram

AU - Studd, James

AU - Broderick, Peter

AU - Kinnersley, Ben

AU - Holroyd, Amy

AU - Law, Philip J.

AU - Kumar, Rajiv

AU - Allan, James M.

AU - Harrison, Christine J.

AU - Moorman, Anthony V.

AU - Vora, Ajay

AU - Roman, Eve

AU - Rachakonda, Sivaramakrishna

AU - Kinsey, Sally E.

AU - Sheridan, Eamonn

AU - Thompson, Pamela D.

AU - Irving, Julie A.

AU - Koehler, Rolf

AU - Hoffmann, Per

AU - Nöthen, Markus M.

AU - Heilmann-Heimbach, Stefanie

AU - Jöckel, Karl Heinz

AU - Easton, Douglas F.

AU - Pharaoh, Paul D.P.

AU - Dunning, Alison M.

AU - Peto, Julian

AU - Canzian, Frederico

AU - Swerdlow, Anthony

AU - Eeles, Rosalind A.

AU - Kote-Jarai, ZSofia

AU - Muir, Kenneth

AU - Pashayan, Nora

AU - Greaves, Mel

AU - Zimmerman, Martin

AU - Bartram, Claus R.

AU - Schrappe, Martin

AU - Stanulla, Martin

AU - Hemminki, Kari

AU - Houlston, Richard S.

AU - Henderson, Brian E.

AU - Haiman, Christopher A.

AU - Benlloch, Sara

AU - Schumacher, Fredrick R.

AU - Olama, Ali Amin Al

AU - Berndt, Sonja I.

AU - Conti, David V.

AU - Wiklund, Fredrik

AU - Chanock, Stephen

AU - Stevens, Victoria L.

AU - Nordestgaard, Børge G.

AU - The Practical Consortium

PY - 2018

Y1 - 2018

N2 - Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.

AB - Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology.

U2 - 10.1038/s41467-018-03178-z

DO - 10.1038/s41467-018-03178-z

M3 - Journal article

C2 - 29632299

AN - SCOPUS:85045221334

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1340

ER -

Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia

Abstract

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