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.
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.
Authors: Sudha K Iyengar; Danhong Song; Barbara E K Klein; Ronald Klein; James H Schick; Jennifer Humphrey; Christopher Millard; Rachel Liptak; Karlie Russo; Gyungah Jun; Kristine E Lee; Bonnie Fijal; Robert C Elston Journal: Am J Hum Genet Date: 2003-12-19 Impact factor: 11.025
Authors: Gwenole Quellec; Stephen R Russell; Johanna M Seddon; Robyn Reynolds; Todd Scheetz; Vinit B Mahajan; Edwin M Stone; Michael D Abràmoff Journal: Invest Ophthalmol Vis Sci Date: 2011-11-25 Impact factor: 4.799
Authors: Pancy O S Tam; Tsz Kin Ng; David T L Liu; Wai Man Chan; Sylvia W Y Chiang; Li Jia Chen; Andrew DeWan; Josephine Hoh; Dennis S C Lam; Chi Pui Pang Journal: Invest Ophthalmol Vis Sci Date: 2008-03-03 Impact factor: 4.799
Authors: Lars G Fritsche; Robert N Fariss; Dwight Stambolian; Gonçalo R Abecasis; Christine A Curcio; Anand Swaroop Journal: Annu Rev Genomics Hum Genet Date: 2014-04-16 Impact factor: 8.929