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Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia

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 fact...

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Autores principales: Lv, Hongchao, Zhang, Mingming, Shang, Zhenwei, Li, Jin, Zhang, Shanshan, Lian, Duan, Zhang, Ruijie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352368/
https://www.ncbi.nlm.nih.gov/pubmed/27903959
http://dx.doi.org/10.18632/oncotarget.13631
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author Lv, Hongchao
Zhang, Mingming
Shang, Zhenwei
Li, Jin
Zhang, Shanshan
Lian, Duan
Zhang, Ruijie
author_facet Lv, Hongchao
Zhang, Mingming
Shang, Zhenwei
Li, Jin
Zhang, Shanshan
Lian, Duan
Zhang, Ruijie
author_sort Lv, Hongchao
collection PubMed
description 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.
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spelling pubmed-53523682017-04-14 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia Lv, Hongchao Zhang, Mingming Shang, Zhenwei Li, Jin Zhang, Shanshan Lian, Duan Zhang, Ruijie Oncotarget Research Paper 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. Impact Journals LLC 2016-11-26 /pmc/articles/PMC5352368/ /pubmed/27903959 http://dx.doi.org/10.18632/oncotarget.13631 Text en Copyright: © 2017 Lv et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lv, Hongchao
Zhang, Mingming
Shang, Zhenwei
Li, Jin
Zhang, Shanshan
Lian, Duan
Zhang, Ruijie
Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia
title Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia
title_full Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia
title_fullStr Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia
title_full_unstemmed Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia
title_short Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia
title_sort genome-wide haplotype association study identify the fgfr2 gene as a risk gene for acute myeloid leukemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352368/
https://www.ncbi.nlm.nih.gov/pubmed/27903959
http://dx.doi.org/10.18632/oncotarget.13631
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