Expanded genome scan in extended families with age-related macular degeneration

Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5453-9. doi: 10.1167/iovs.06-0655.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 3 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Family Health
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Humans
  • Lod Score
  • Macular Degeneration / genetics*
  • Microsatellite Repeats
  • Pedigree