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DOI | 10.1038/s41467-017-01884-8 |
Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics | |
Speedy, Helen E.1; Beekman, Renee2,3; Chapaprieta, Vicente4; Orlando, Giulia1; Law, Philip J.1; Martin-Garcia, David2,3; Gutierrez-Abril, Jesus5; Catovsky, Daniel1; Bea, Silvia2,3; Clot, Guillem2,3; Puiggros, Montserrat6; Torrents, David6,7; Puente, Xose S.3,5; Allan, James M.8; Lopez-Otin, Carlos3,5; Campo, Elias2,3,4,9; Houlston, Richard S.1; Martin-Subero, Jose, I2,3,4,7 | |
2019-08-09 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | England; Spain |
英文摘要 | Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000480234600006 |
WOS关键词 | GENOME-WIDE ASSOCIATION ; READ ALIGNMENT ; RISK LOCI ; IMPUTATION ; TARGET |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203552 |
专题 | 资源环境科学 |
作者单位 | 1.Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England; 2.Inst Invest Biomed August Pi & Sunyer IDIBAP, Barcelona 08036, Spain; 3.Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain; 4.Univ Barcelona, Dept Fonaments Clin, Fac Med, E-08036 Barcelona, Spain; 5.Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol IUOPA, E-33006 Oviedo, Spain; 6.Univ Barcelona, Programa Conjunto Biol Computac, BSC, Spanish Natl Bioinformat Inst,IRB, Barcelona, Spain; 7.ICREA, Barcelona 08010, Spain; 8.Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England; 9.Hosp Clin Barcelona, Hematopathol Sect, E-08036 Barcelona, Spain |
推荐引用方式 GB/T 7714 | Speedy, Helen E.,Beekman, Renee,Chapaprieta, Vicente,et al. Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Speedy, Helen E..,Beekman, Renee.,Chapaprieta, Vicente.,Orlando, Giulia.,Law, Philip J..,...&Martin-Subero, Jose, I.(2019).Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.NATURE COMMUNICATIONS,10. |
MLA | Speedy, Helen E.,et al."Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics".NATURE COMMUNICATIONS 10(2019). |
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