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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Jayaram Vijayakrishnan
  • M. Y.R. Henrion
  • A V Moorman
  • P Sivaramakrishna Rachakonda
  • Ismail Hosen
  • M. I. Da Silva Filho
  • A Holroyd
  • Sara E. Dobbins
  • Rolf Koehler
  • Julie A Irving
  • J M Allan
  • Tracy Lightfoot
  • Erika Roman
  • Sally E Kinsey
  • Eamonn Sheridan
  • P. D. Thompson
  • P Hoffmann
  • M M Nöthen
  • Stefanie Heilmann-Heimbach
  • Karl-Heinz Jöckel
  • M. W. Greaves
  • C J Harrison
  • C R Bartram
  • Martin Schrappe
  • Martin Stanulla
  • R S Houlston
Organisations
External organisations
  • Institute of Cancer Research London
  • German Cancer Research Centre
  • University of Newcastle upon Tyne
  • Heidelberg University
  • University of York
  • Leeds General Infirmary
  • University of Leeds
  • University of Manchester
  • University of Bonn
  • University Hospital Basel
  • University Hospital Essen
  • University Medical Center Schleswig-Holstein Campus Kiel
  • Hannover Medical School
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)573-579
Number of pages7
JournalLeukemia
Volume31
Issue number3
Publication statusPublished - 2017 Mar 1
Publication categoryResearch
Peer-reviewedYes