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C. L. Thompson, B. E. K. Klein, R. Klein, J. Capriotti, D. Leontiev, K. E. Lee, S. K. Iyengar; The 10q26 Region and Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3239.
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Age-related macular degeneration (AMD) is a leading cause of blindness in developed nations. The 10q26 region has been linked to AMD in multiple samples and has also been reported as most significantly coupled to AMD in a recent meta-analysis. Others have reported highly significant associations between the PLEKHA1/LOC387715 locus and AMD.
We chose to investigate this region further with two additional independent datasets. The first sample, the Family Age Related Maculopathy Study (FARMS) consisted of 297 individuals in 34 families ascertained through a single individual with severe AMD. Individuals in the FARMS sample were genotyped at 45 single nucleotide polymorphisms (SNPs) in the 10q26 region. The second is a population-based sample, the Beaver Dam Eye Study (BDES), consisting of 2273 individuals genotyped at four SNPs in the PLEKHA1 and LOC387715 genes. All individuals in both studies were assigned values for four scales representing the severity of different aspect of AMD - 15-step AMD, 6-step pigmentary abnormality, 6-step drusen size and 4-step drusen type scales. Associations were performed via a regression model accounting for age and familial correlations as implemented in ASSOC (S.A.G.E. 2005).
Strong evidence continues to exist for the association of this region to AMD, with intergenic markers showing the lowest p-values in the FARMS sample (p < 10-7 at the rs2223089 SNP). This SNP is also highly significant for drusen size (p= 3.5 x 10-5) and borderline significantly associated with drusen type (p=0.01). The BDES sample showed highly significant p-values at all four SNPs evaluated. All four scales provided strong evidence of association of this region in the BDES sample.
These results support evidence of a single or multiple variations in this region affecting AMD development. From this analysis, it appears that the intragenic region is most significantly associated with AMD and AMD-related phenotypes. More work will need to be done to narrow the region and explain the biological significance.
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