IOVS Journal of Clinical Microbiology
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(Investigative Ophthalmology and Visual Science. 2006;47:5453-5459.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0655
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Expanded Genome Scan in Extended Families with Age-Related Macular Degeneration

Sandra Barral,1 Peter J. Francis,2 Dennis W. Schultz,2 Mitchell B. Schain,2 Chad Haynes,1 Jacek Majewski,1 Jurg Ott,1 Ted Acott,2 Richard G. Weleber,2 and Michael L. Klein2

1From the Laboratory of Statistical Genetics, Rockefeller University, New York, New York; and the 2Macular Degeneration Center, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon.

PURPOSE. To investigate further the genetic contribution to age-related macular degeneration (AMD), increasing the power of a previous analysis and reproducing the original findings.

METHODS. A large cohort of families with this condition was assembled, and an expanded genome scan was performed with 556 microsatellite markers. In 2003, the results were reported of a genome-wide linkage analysis of 70 of these pedigrees. Members of 51 new families have now been ascertained and many of the original pedigrees expanded. Parametric and nonparametric linkage analyses were performed with a denser map of markers. In addition, analyses were performed with the sample stratified by age at ascertainment and by two major advanced phenotypes for the disease: neovascular AMD (choroidal neovascularization) and geographic atrophy.

RESULTS. The results corroborate the macular degeneration–susceptibility loci consistently reported by the authors and others in genome-wide scans. New loci were identified, including the finding of a two-point HLOD of 3.70 at 6q25.2.

CONCLUSIONS. The results suggest that the use of families enriched in predisposition to AMD has legitimacy. Genetic analyses of a genome-wide scan performed on our large cohort of families add further confirmatory evidence that susceptibility loci lie on 1q, 3p, 9q, and 10q. Furthermore, new loci have been identified, including a locus on 6q.




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A. Swaroop, K. E. Branham, W. Chen, and G. Abecasis
Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits
Hum. Mol. Genet., October 15, 2007; 16(R2): R174 - R182.
[Abstract] [Full Text] [PDF]


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