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R.R. Allingham, J.L. Wiggs, F.L. Graham, K.R. Larocque–Abramson, C. Santiago–Turla, A. Ventura, J.L. Haines, M.A. Pericak–Vance, M.A. Hauser; A High Density Linkage Screen for POAG: Evidence for Different Loci by Race . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3258.
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© ARVO (1962-2015); The Authors (2016-present)
Primary open–angle glaucoma (POAG) is a common complex inherited disorder. Here we report a major SNP–based genome–wide screen on a large POAG family dataset.
A genome–wide screen was performed on 142 multiplex POAG families each containing 2 or more affected family members. The marker panel consisted of 5067 single nucleotide polymorphisms (SNPs) (Linkage Panel IV) and was performed utilizing the Illumina Bead Station platform. Two–point and multipoint heterogeneity lod scores were calculated using Allegro. For multipoint analyses a single SNP was selected from each bin of SNPs in linkage disequilibrium (r2 > 0.16). Genotype data were analyzed in toto and after stratification by Caucasian and African–American race.
The multiplex POAG family dataset contained 142 families (including 87 Caucasian, 37 African–American families). The genome–wide screen produced approximately 2.7 million genotypes for analysis. The two–point analyses was performed on the total dataset. For multipoint analyses the Caucasian and African–American family subsets were also analyzed. Peak two–point MLOD scores for chromosomes 3, 6, 14, and 15 were 4.4, 2.6, 4.4, and 3.5, respectively. Peak multipoint (parametric or non–parametric) lod scores for chromosomes 3, 6, 14, and 15 were 2.6, 1.7, 2.1, and 2.6, respectively. Additional multipoint lod scores > 2.0 were found on chromosomes 12 (2.2) and 17 (2.0). Multipoint lod scores for the loci on chromosomes 3, 14, and 15 were primarily obtained from the African–American subset. The lod score for the locus on chromosome 12 was derived from the Caucasian subset. Contributions from both racial subsets contributed to the lod scores on chromosomes 6 and 17.
We have performed the most definitive genome–wide linkage screen for POAG described to date, using over 5000 markers in one of the largest reported multiplex family datasets. For the first time we report known and novel chromosomal loci for POAG that appear to be derived primarily from either Caucasian or African–American family subsets. These findings suggest that different genetic loci may in part explain variations in the prevalence and phenotype of POAG among races described in population–based studies.
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