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A. S. Hoguet, E. DelBono, R. R. Allingham, M. A. Hauser, M. Pericak-Vance, J. L. Haines, J. L. Wiggs; Fine Mapping of GLC1K Primary Open Angle Glaucoma Region. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1724. doi: https://doi.org/.
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We previously identified a locus on chromosome 20p12 associated with juvenile-onset primary open angle glaucoma (JOAG), designated GLC1K. Further genome studies using 5,067 SNPs also demonstrated suggestive linkage to this region in a set of 124 families affected by adult-onset primary open angle glaucoma (POAG; LOD>2.0). The purpose of this study is to perform haplotype analyses and association analyses to refine this region and identify candidate genes for POAG and JOAG.
SNP genotype data from a SNP-based genome scan (Illumina) using 124 families with POAG was analyzed to refine the linkage region on chromosome 20. 295 POAG patients and 122 controls were used for case/control association analysis. 40 SNPs distributed within the above refined region were evaluated for association in the case/control cohort using a quantitative PCR approach (TaqMan assay) by calculating a chi square distribution for genotype and allele frequency.
SNP haplotype analysis showed that 66% (n=82) of families had a consistent haplotype among affected family members. Of these, 7 families had 4 or more affected members, and of these 4 families shared the same haplotype between SNPs rs1040756 and rs466243 and 3 shared the same haplotype between SNPs rs775133 and rs2077147, identifying a region of 4.2Mb that is likely to contain the causative gene. Within this region, association studies revealed 2 SNPs, rs424792 (chr20:15,031,889bp) and rs3790316 (chr20:17,577,439bp) that showed significant association with POAG for genotype (p=0.002 and 0.4X10-4 respectively) and allele frequency (p=0.003 and 0.005 respectively).
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