Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.

Bibliographic Details
Title: Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.
Authors: Andrew J P Smith, Philip Howard, Sonia Shah, Per Eriksson, Stefan Stender, Claudia Giambartolomei, Lasse Folkersen, Anne Tybjærg-Hansen, Meena Kumari, Jutta Palmen, Aroon D Hingorani, Philippa J Talmud, Steve E Humphries
Source: PLoS Genetics, Vol 8, Iss 8, p e1002908 (2012)
Publisher Information: Public Library of Science (PLoS), 2012.
Publication Year: 2012
Collection: LCC:Genetics
Subject Terms: Genetics, QH426-470
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1553-7390
1553-7404
Relation: https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002908&type=printable; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404
DOI: 10.1371/journal.pgen.1002908&type=printable
DOI: 10.1371/journal.pgen.1002908
Access URL: https://doaj.org/article/5e4c591f9f444fc788fb8731f0d5bd0c
Accession Number: edsdoj.5e4c591f9f444fc788fb8731f0d5bd0c
Database: Directory of Open Access Journals
More Details
ISSN:15537390
15537404
DOI:10.1371/journal.pgen.1002908&type=printable
Published in:PLoS Genetics
Language:English