期刊
PLOS GENETICS
卷 8, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002908
关键词
-
资金
- British Heart Foundation (BHF) [PG/07/133/24260, RG/08/014, SP/07/007/23671]
- National Heart, Lung, and Blood Institute [NHLBI: HL36310]
- Medical Research Council
- British Heart Foundation
- Health and Safety Executive
- Department of Health
- National Institute on Aging [AG13196]
- NIH
- Agency for Health Care Policy Research [HS06516]
- John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-Economic Status and Health
- Swedish Research Council [12660]
- European Commission (FAD) [Health F2 2008 200647]
- Danish Medical Research Council [10-083788]
- Research Fund at Rigshospitalet
- Copenhagen University Hospital
- Chief Physician Johan Boserup and Lise Boserup's Fund
- Ingeborg and Leo Dannin's Grant
- Henry Hansen's and Wife's grant
- Order of Odd Fellows
- [FS/2005/125]
- British Heart Foundation [RG/08/008/25291, SP/07/007/23671] Funding Source: researchfish
Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising large-scale genotyping technology (FAIRE-gen) to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-alpha), rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006), and analysis of gene expression identified an allelic association with LXR-alpha expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据