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Xiaoyi Gao, Yutao Liu, W. James Gauderman, Mina Torres, Talin Haritunians, Jane Kuo, Kent Taylor, Jerome Rotter, Rohit Varma; Fine mapping of the RXRA-COL5A1 locus for central corneal thickness. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6210.
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Central corneal thickness (CCT) is associated with vision disorders including glaucoma and keratoconus. Multiple studies have reported the association of the RXRA-COL5A1 locus on chromosome 9 with CCT. Here we describe in silico fine mapping, followed by expression analysis.
We conducted this research using current GWAS data from the Los Angeles Latino Eye Study (n = 1,800). All Latino subjects were age 40 years and older. We carried out regional genotype imputation over the RXRA-COL5A1 locus based on the 1000 Genomes Project reference panels and retained only SNPs of high imputation quality with MACH Rsq greater than 0.80. We performed single-marker and conditional analyses with adjustment for age, sex and principal components of genetic ancestry. We also performed expression analysis using human ocular tissues.
We replicated several previously reported SNPs within the RXRA-COL5A1 region and discovered a novel SNP, rs3118515 (P = 8.25E-10) in the uncharacterized LOC100506532 (gene type: miscRNA), that better captures the association with CCT in Latinos. Conditional analysis demonstrated that rs3118515 is responsible for the association of the RXRA-COL5A1 locus. Multiple sources of ENCODE evidence suggest that rs3118515 is in a regulatory region. Reverse-transcription PCR products indicated that transcripts of LOC100506532 surrounding rs3118515 were expressed in human cornea.
Fine mapping and expression analysis improved the localization and the annotation of SNPs that regulate CCT at the RXRA-COL5A1 locus, indicating the involvement of LOC100506532 and offering insights in the molecular mechanism of CCT.
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