DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Acute lymphoblastic leukemia (childhood). The EFO term acute lymphoblastic leukemia was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: acute lymphoblastic leukemia

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

E Ellinghaus, M Stanulla, G Richter, D Ellinghaus, G te Kronnie, G Cario, G Cazzaniga, M Horstmann, R Panzer Grümayer, H Cavé, J Trka, O Cinek, A Teigler-Schlegel, A ElSharawy, R Häsler, A Nebel, B Meissner, T Bartram, F Lescai, C Franceschi, M Giordan, P Nürnberg, B Heinzow, M Zimmermann, S Schreiber, M Schrappe, A Franke

TITLE:

Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.

JOURNAL:

Leukemia May 2012, Vol 26, pp. 902-9

ABSTRACT:

Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) - the most common chromosomal translocation observed in childhood ALL - which leads to an ETV6-RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, P(CMH)=8.94 × 10(-9), OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10(-11), OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10(-9), OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10(-7), OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6-RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis. PUBMED: 22076464
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