The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences.
BACKGROUND
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood.


OBJECTIVE
To investigate the impact of genetic and environmental factors.


METHODS
Living twins in the National Academy of Sciences-National Research Council World War II Veteran Twin Registry born between 1917 and 1927.


METHODS
Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effects was employed to partition variation in liability to AMD and signs of maculopathy into additive genetic, common environment, and unique environment components.


METHODS
Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs.


RESULTS
Of the 840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had intermediate AMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significant genetic (0.26-0.71) and unique environmental (0.28-0.64) proportions of variance were detected.


CONCLUSIONS
Genetic factors play a substantial role in the etiology of AMD and associated macular characteristics, explaining 46% to 71% of the variation in the overall severity of the disease. Environmental factors unique to each twin also contribute to the occurrence of this disease. This quantification of relative genetic and environmental contributions to the development of AMD should guide future research on this important cause of blindness.
Seddon
Johanna M
JM
Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Department of Opthalmology, Harvaed Medical School, Boston, MA 02114, USA. Johanna_Seddon@meei.harvard.edu
Cote
Jennifer
J
Page
William F
WF
Aggen
Steven H
SH
Neale
Michael C
MC
D000368:Aged; D004200:Diseases in Twins / Q000453:epidemiology / Q000235:genetics*; D004777:Environment; D006801:Humans; D008268:Macular Degeneration / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D015995:Prevalence; D012042:Registries; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014481:United States / Q000453:epidemiology