Genetic influence on early age-related maculopathy: a twin study

Ophthalmology. 2002 Apr;109(4):730-6. doi: 10.1016/s0161-6420(01)01049-1.


Objective: Age-related macular degeneration (AMD) is the most common cause of blindness in industrialized countries. There has been considerable interest in the genetics of early age-related maculopathy (ARM) and AMD, because they have phenotypes similar to inherited diseases where mutations have been identified, but the heritability of ARM and AMD is unknown.

Design: A classical twin study was performed to compare the concordance in monozygotic (MZ) and dizygotic (DZ) twins in an unselected sample of female volunteer twins.

Participants: Five hundred six twin pairs, 226 MZ and 280 DZ, with a mean age of 62 years, were examined.

Methods: ARM was graded from stereoscopic macular photographs of 501 of the twin pairs (99%) according to the International ARM Epidemiologic Study Group grading system. The casewise concordance was calculated for twin pairs from 2 x 2 contingency tables of affected/unaffected twins, and these tables were used in maximum likelihood genetic modeling to estimate the heritabilities of phenotypes graded.

Main outcome measures: Prevalence of ARM; concordance in MZ and DZ twins of the phenotypes of ARM, soft drusen >63 microm and > or =125 microm diameter, pigmentary changes and hard drusen (<20 and > or =20 in number); heritability of ARM and subphenotypes.

Results: The overall prevalence of ARM was 14.6% (95% confidence interval [CI], 12.4%-16.8%). The concordance for ARM in MZ twins was 0.37 compared with 0.19 in DZ twins, suggesting a role for genes. Modeling confirmed a genetic effect for phenotypes of ARM, soft drusen, pigmentary changes, and > or =20 hard drusen, although there was little genetic effect for scattered (<20) hard drusen. The heritability of ARM was estimated as 45% (95% CI, 35%-53%). The most heritable phenotypes were soft drusen > or =125 microm (57%) and > or =20 hard drusen (81%), with the latter being dominantly inherited.

Conclusions: This study confirms a significant genetic influence in ARM and suggests that future genetic studies should examine phenotypes of large (> or =125 microm) soft drusen and > or =20 hard drusen, because these seem to be the most heritable components.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Diseases in Twins / genetics*
  • England / epidemiology
  • Humans
  • Macular Degeneration / diagnosis
  • Macular Degeneration / epidemiology
  • Macular Degeneration / genetics*
  • Middle Aged
  • Phenotype
  • Prevalence
  • Twins, Dizygotic*
  • Twins, Monozygotic*