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. 2017 Mar;31(3):573-579.
doi: 10.1038/leu.2016.271. Epub 2016 Oct 3.

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

J Vijayakrishnan  1 , R Kumar  2 , M Y R Henrion  1 , A V Moorman  3 , P S Rachakonda  2 , I Hosen  2 , M I da Silva Filho  2 , A Holroyd  1 , S E Dobbins  1 , R Koehler  4 , H Thomsen  2 , J A Irving  3 , J M Allan  3 , T Lightfoot  5 , E Roman  5 , S E Kinsey  6 , E Sheridan  7 , P D Thompson  8 , P Hoffmann  9   10 , M M Nöthen  9 , S Heilmann-Heimbach  9 , K H Jöckel  11 , M Greaves  12 , C J Harrison  3 , C R Bartram  4 , M Schrappe  13 , M Stanulla  14 , K Hemminki  2   15 , R S Houlston  1
Affiliations

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

J Vijayakrishnan et al. Leukemia. 2017 Mar.

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Regional plots of association results and recombination rates for the newly identified risk loci for BCP-ALL (a and b). Results for 10q26.13 (rs35837782, a) and 12q23.1 (rs4762284, b). Plots (using visPig) show association results of both genotyped (triangles) and imputed (circles) SNPs in the GWAS samples and recombination rates. −log10 P-values (y axes) of the SNPs are shown according to their chromosomal positions (x axes). The sentinel SNP in each combined analysis is shown as a large circle or triangle, and is labeled by its rsID. The color intensity of each symbol reflects the extent of LD with the top genotyped SNP, white (r2=0) through to dark red (r2=1.0). Genetic recombination rates, estimated using UK10K Genomes Project samples, are shown with a light-blue line. Physical positions are based on NCBI build 37 of the human genome. Also shown are the relative positions of genes and transcripts mapping to the region of association. Genes have been redrawn to show their relative positions; therefore, maps are not to physical scale. The lower panel is the chromatin-state segmentation track (ChromHMM) for lymphoblastoid cells using data from the HapMap ENCODE Project. CNV, copy-number variation.
See this image and copyright information in PMC

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