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

The PRACTICAL Consortium

doi:10.1038/s41467-018-03178-z

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

The PRACTICAL Consortium

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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
DOIs	https://doi.org/10.1038/s41467-018-03178-z
State	Published - 1 Dec 2018

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@article{11c09ccf1d7f44f9ba0d401dedce9cbe,

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 = "{The PRACTICAL Consortium} and 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 Barry Rosenstein",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-03178-z",

language = "English",

volume = "9",

journal = "Nature Communications",

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T1 - Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia

AU - The PRACTICAL Consortium

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 - Rosenstein, Barry

PY - 2018/12/1

Y1 - 2018/12/1

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.

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U2 - 10.1038/s41467-018-03178-z

DO - 10.1038/s41467-018-03178-z

M3 - 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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