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A Swaroop, BM Yashar, N Ghiasvand, S Yoshida, S Zareparsi, H Stringham, J Richards, M Boehnke, S Jacobson, G Abecasis; Identification of Susceptibility Genes for Age-related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):832.
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Purpose: Identification of genetic loci that determine susceptibility to Age-related macular degeneration (AMD). Methods: We identified individuals with AMD from the patient population of the Retina Research Group. Based on oral family histories, multiple families (N=129) were identified with greater than 2 affected individuals. Both affected and unaffected individuals (N = 539) in these families were enrolled in the AMD Family Studies Core. Following informed consent, we obtained blood samples and documentation of ophthalmic findings (retinal evaluation and fundus photography). Families were selected for analysis based on the patterns of inheritance of disease and the concordance of clinical phenotypes. We employed genome wide scans on all affected and unaffected individuals and carried out both parametric and nonparametric multipoint linkage analyses. Results: Three families (A, B, C) were selected for analysis based on the inter-familial concordance of clinical phenotypes. In Families A and B, the disease manifests as primarily exudative AMD, while in Family C all affected individuals have atrophic disease. Multipoint analyses have excluded the majority of known retinal and macular disease genes and loci, the majority of chromosomes and revealed significant positive LOD scores (≷2) at two independent genomic intervals in Family A and Family C. Analysis of these families jointly and separately suggested that distinct genomic intervals were associated with the disease phenotypes. Haplotypes were constructed in the two intervals in Family C. These were consistent with the multipoint analysis and narrowed the genomic intervals to 9.08 cM and 6.7 cM. Results of candidate gene screens will be discussed, along with mapping results from Family B and additional families with concordant phenotypes. Conclusion: Our genome screens have identified genomic intervals that may contain candidate AMD susceptibility genes. These regions are distinct from previously implicated genomic intervals and may be important in defining the genetic complexity of this common disease.
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