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. 2017 Jan 31;8(5):7891-7899.
doi: 10.18632/oncotarget.13631.

Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia

Hongchao Lv  1 , Mingming Zhang  1 , Zhenwei Shang  1 , Jin Li  1 , Shanshan Zhang  2 , Duan Lian  1 , Ruijie Zhang  1
Affiliations

Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia

Hongchao Lv et al. Oncotarget. .

Abstract

Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, and generally considered to be caused by environment and genetic factors. In this study, we combined a genome-wide haplotype association study (GWHAS) and gene prioritization strategy to mine AML-related genetic affect factors and understand its pathogenesis. A total of 175 AML patients were downloaded from the public GEO database (GSE32462) and 218 matched Caucasian controls were from the HapMap Project. We first identified the linkage disequilibrium (LD) blocks and performed a GWHAS to scan AML-related haplotypes. Then we mapped these haplotypes to the corresponding genes as candidate. And finally, we prioritized all the AML candidate genes based on the similarity with 38 known AML susceptibility genes. The results showed that 1754 haplotypes were significant associated with AML (P<1E-5) and mapped to 591 candidate genes. After prioritizing all 591 AML candidate genes, we obtained four genes ranking at the front as AML risk genes: RUNX1, JAK1, PDGFRA, and FGFR2. Among them, RUNX1, JAK1 and PDGFRA had been confirmed as AML risk genes. In particular, we found that the gene FGFR2 was a novel AML susceptibility gene with a haplotype TT (rs7090018 and rs2912759) showed significant association with AML (P-value = 7.07E-06). In a word, our findings might provide a new perspective to understand the pathogenesis of AML.

Keywords: acute myeloid leukemia; gene prioritization; haplotype.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. The haplotype analysis result of RUNX1 gene
Figure 2
Figure 2. The haplotype analysis result of JAK1 gene
Figure 3
Figure 3. The haplotype analysis result of PDGFRA gene
Figure 4
Figure 4. The haplotype analysis result of FGFR2 gene
See this image and copyright information in PMC

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