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

Vijayakrishnan, Jayaram; Kumar, R. LU ; Henrion, M. Y.R.; Moorman, A V; Rachakonda, P Sivaramakrishna; Hosen, Ismail; Da Silva Filho, M. I. LU ; Holroyd, A; Dobbins, Sara E. and Koehler, Rolf, et al. (2017) In Leukemia 31(3). p.573-579
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... (More)

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.

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Leukemia
volume
31
issue
3
pages
7 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:84994700875
  • wos:000395887600007
ISSN
0887-6924
DOI
10.1038/leu.2016.271
language
English
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yes
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2aa64163-6feb-45fd-ab89-136e0f912ba9
date added to LUP
2017-10-26 08:59:43
date last changed
2018-01-16 13:24:17
@article{2aa64163-6feb-45fd-ab89-136e0f912ba9,
  abstract     = {<p>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<sup>-11</sup>) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10<sup>-</sup>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.</p>},
  author       = {Vijayakrishnan, Jayaram and Kumar, R. and Henrion, M. Y.R. and Moorman, A V and Rachakonda, P Sivaramakrishna and Hosen, Ismail and Da Silva Filho, M. I. and Holroyd, A and Dobbins, Sara E. and Koehler, Rolf and Thomsen, H. and Irving, Julie A and Allan, J M and Lightfoot, Tracy and Roman, Erika and Kinsey, Sally E and Sheridan, Eamonn and Thompson, P. D. and Hoffmann, P and Nöthen, M M and Heilmann-Heimbach, Stefanie and Jöckel, Karl-Heinz and Greaves, M. W. and Harrison, C J and Bartram, C R and Schrappe, Martin and Stanulla, Martin and Hemminki, K. and Houlston, R S},
  issn         = {0887-6924},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {573--579},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1},
  url          = {http://dx.doi.org/10.1038/leu.2016.271},
  volume       = {31},
  year         = {2017},
}