Use of Allele-Specific FAIRE to Determine Functional Regulatory Polymorphism Using Large-Scale Genotyping Arrays

Smith, Andrew J. P., Howard, Philip, Shah, Sonia, Eriksson, Per, Stender, Stefan, Giambartolomei, Claudia, Folkersen, Lasse, Tybjaerg-Hansen, Anne, Kumari, Meena, Palmen, Jutta, Hingorani, Aroon D., Talmud, Philippa J. and Humphries, Steve E. (2012) Use of Allele-Specific FAIRE to Determine Functional Regulatory Polymorphism Using Large-Scale Genotyping Arrays. PLoS Genetics, 8 8: e1002908.1-e1002908.10. doi:10.1371/journal.pgen.1002908


Author Smith, Andrew J. P.
Howard, Philip
Shah, Sonia
Eriksson, Per
Stender, Stefan
Giambartolomei, Claudia
Folkersen, Lasse
Tybjaerg-Hansen, Anne
Kumari, Meena
Palmen, Jutta
Hingorani, Aroon D.
Talmud, Philippa J.
Humphries, Steve E.
Title Use of Allele-Specific FAIRE to Determine Functional Regulatory Polymorphism Using Large-Scale Genotyping Arrays
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2012-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1002908
Open Access Status DOI
Volume 8
Issue 8
Start page e1002908.1
End page e1002908.10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract 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-α), 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-α 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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID PG/07/133/24260
NHLBI: HL36310
AG13196
HS06516
12660
Health F2 2008 200647
10-083788
FS/2005/125
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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