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J.M. Seddon, K. Book, S. Chong, J. Cote, S.L. Santangelo; A Genome-Wide Scan for Age-Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1781.
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Purpose: There is ample evidence that age-related macular degeneration has a familial/genetic component. We report the results of a genome-wide scan of 158 multiplex families. Methods: AMD classification was based on fundus photography and was assigned a grade ranging from 1 (no disease) to 5 (exudative disease) according to a modified grading system used in the Age-Related Eye Disease Study. Genotyping was performed by the NHLBI Mammalian Genotyping Service at Marshfield (404 short tandem repeat markers, Weber Screening Set 10). The sample included 158 families with 2 or more siblings with AMD, 479 affected individuals (grade 3 or higher), 138 unaffected (grades 1 or 2 over age 60), and 11 whose affection status was unknown (grades 1 or 2, under age 60). Relative pairs included 514 affected sibling, 28 avuncular, 53 cousin, 7 grandparent-grandchild, and 9 grand avuncular pairs. Two-point parametric (FASTLINK) and multipoint parametric and nonparametric (GENEHUNTER, MERLIN+SimWalk2) analyses were performed. Results: Maximum 2-point LOD scores ranging from 1.0 – 2.0 were found for markers on Chr 1,2,8,10,14,15 and 22. Multipoint analyses were consistent with the 2-point results for Chr 1,2,8,10 and 22 and provided evidence for additional regions of linkage on Chr 3,6,8,12,16 and X. Multipoint heterogeneity LODs =2.4 were found on Chr1 and 2. Our strongest evidence for linkage was found on chromosomes 2 (1 marker), 3 (2 adjacent markers), 8 (7 contiguous markers), and 6 (2 adjacent markers), with empirical p-values = 0.00001 using MERLIN+SimWalk2. Conclusions: Our genome-wide scan for AMD indicated several regions, with internally consistent evidence (from 2-point and/or multipoint, parametric and nonparametric analyses), for linkage to regions on chromosomes 1, 2, 3, 8, 10, 12, 16, and 22; regions on chromosomes 6 and X were identified by only one of the multipoint analysis methods. Significant evidence for linkage was found by one multipoint method for regions on chromosomes 2, 3, 6 and 8.
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