TY - JOUR
T1 - Expanded genome scan in extended families with age-related macular degeneration
AU - Barral, Sandra
AU - Francis, Peter J.
AU - Schultz, Dennis W.
AU - Schain, Mitchell B.
AU - Haynes, Chad
AU - Majewski, Jacek
AU - Ott, Jurg
AU - Acott, Ted
AU - Weleber, Richard G.
AU - Klein, Michael L.
PY - 2006/12
Y1 - 2006/12
N2 - 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 non-parametric 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.
AB - 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 non-parametric 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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U2 - 10.1167/iovs.06-0655
DO - 10.1167/iovs.06-0655
M3 - Article
C2 - 17122136
AN - SCOPUS:33947615435
SN - 0146-0404
VL - 47
SP - 5453
EP - 5459
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 12
ER -