The US Twin Study of Age-Related Macular Degeneration

Seddon, Johanna M.; Côté, Jean-Charles; Page, William F.; Aggen, Steven H.; Neale, Michael C.

doi:10.1001/archopht.123.3.321

Cited by 379 publications

(145 citation statements)

References 56 publications

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“…In a study based on 406 twin pairs with 226 monozygotic and 280 dizygotic twins, Hammond et al [18] calculated a heritability of age-related maculopathy and late AMD of 0.45 and 0.81, respectively. This was confirmed by Seddon et al [20] based on the analysis of 840 elderly male twins including 210 monozygotic and 181 dizygotic complete twin pairs and 58 singletons, showing heritability rates for grade 3 and 5 AMD of 0.67 and 0.71, respectively.…”

Section: Genetic Studiessupporting

confidence: 62%

“…Indeed, a higher concordance rate of AMD has been demonstrated in both study designs including monozygotic twins or relatives of AMD patients. Twin studies have strongly suggested underlying genetic factors in AMD, showing that the concordance of the disease was higher among monozygotic than dizigotic twins [15,16,17,18,19,20]. In a study based on 406 twin pairs with 226 monozygotic and 280 dizygotic twins, Hammond et al [18] calculated a heritability of age-related maculopathy and late AMD of 0.45 and 0.81, respectively.…”

Section: Genetic Studiesmentioning

confidence: 99%

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Genetic Factors Associated with Age-Related Macular Degeneration

et al. 2011

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Section: Genetic Studiessupporting

confidence: 62%

Section: Genetic Studiesmentioning

confidence: 99%

Genetic Factors Associated with Age-Related Macular Degeneration

et al. 2011

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“…These variants were identified using the xBrowse software to filter variants by the following stringent criteria: (1) had a minor allele frequency (MAF) of < 0.1% in the 1000 Genomes Project and Exome Aggregation Consortium (ExAC) databases, (2) belonged to a potentially damaging functional annotation class, (3) was predicted in silico to have a functional impact on protein function, and (4) followed the inheritance pattern of the disease within the family.…”

Section: Resultsmentioning

confidence: 99%

“…The disease affects the central region of the retina, resulting in progressive visual impairment and reduced quality of life. AMD is highly heritable and twin studies have shown that between 46% and 71% of phenotypic variance is explained by genetic factors 1,2 . Several environmental and genetic components contribute to its multifactorial etiology 2 .…”

mentioning

confidence: 99%

Mapping rare, deleterious mutations in Factor H: Association with early onset, drusen burden, and lower antigenic levels in familial AMD

et al. 2016

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The genetic architecture of age-related macular degeneration (AMD) involves numerous genetic variants, both common and rare, in the coding region of complement factor H (CFH). While these variants explain high disease burden in some families, they fail to explain the pathology in all. We selected families whose AMD was unexplained by known variants and performed whole exome sequencing to probe for other rare, highly penetrant variants. We identified four rare loss-of-function variants in CFH associated with AMD. Missense variant CFH 1:196646753 (C192F) segregated perfectly within a family characterized by advanced AMD and drusen temporal to the macula. Two families, each comprising a pair of affected siblings with extensive extramacular drusen, carried essential splice site variant CFH 1:196648924 (IVS6+1G>A) or missense variant rs139360826 (R175P). In a fourth family, missense variant rs121913058 (R127H) was associated with AMD. Most carriers had early onset bilateral advanced AMD and extramacular drusen. Carriers tended to have low serum Factor H levels, especially carriers of the splice variant. One missense variant (R127H) has been previously shown not to be secreted. The two other missense variants were produced recombinantly: compared to wild type, one (R175P) had no functional activity and the other (C192F) had decreased secretion.Age-related macular degeneration (AMD), an irreversible degenerative disease, is the leading cause of blindness in adults over the age of 60. The disease affects the central region of the retina, resulting in progressive visual impairment and reduced quality of life. AMD is highly heritable and twin studies have shown that between 46% and 71% of phenotypic variance is explained by genetic factors 1,2 . Several environmental and genetic components contribute to its multifactorial etiology 2 . Early genome-wide scans for evidence of linkage in AMD families revealed several signals including one mapping to the long (q) arm of chromosome 1 [3][4][5] . Investigation of the genetic architecture of AMD subsequently evolved over the next 15 years on population, family, and individual levels. Genome-wide association studies (GWAS) and meta-GWAS efforts identified numerous genetic variants in over 20 different genes showing an association with AMD risk, including a common variant in the coding region of complement factor H (CFH) (RefSeq

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“…Age was observed to be the main risk factor for AMD in the Beaver Dam, Blue Mountains, and Rotterdam epidemiologic studies [3,4]. However, specific risk factors of AMD have been suggested or recognized, such as genetic allelic predisposition [5,6], female gender [7], hypertension and history of cardiovascular disease [8], smoking [9], high body mass index [10], and a diet rich in meat and lipids [11]. In developed countries, life expectancy has increased significantly during the past 20 years [12], but at the same time, exposure to many of the recognized environmental risk factors for AMD also increased during this period.…”

Section: Introductionmentioning

confidence: 99%

Age at Occurrence of Exudative Age-Related Macular Degeneration in a Clinical Setting: Difference between 1986 and 2006

Cohen

Dubois²,

Tadayoni³

et al. 2010

Ophthalmologica

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Purpose: To our knowledge, there is no published study on the evolution of age of occurrence of exudative age-related macular degeneration (AMD). The present study was performed to test whether or not the average age of patients with newly diagnosed choroidal neovascularization (CNV) due to AMD has changed in a clinical setting during the past 20 years. Methods: Nonrandomized comparative case study. Charts and fluorescein angiograms of consecutive patients diagnosed in 1986 and 2006 in a tertiary care center were analyzed to identify differences in age, gender and type of CNV. Mann-Whitney’s nonparametric test was used to compare the statistical distribution of the parameters. χ² or Fisher’s exact test was used for categorical variables. Results: 357 patients with CNV due to AMD, 79 in 1986, and 278 in 2006 were included. The patients diagnosed in 2006 were 4.7 years older than those diagnosed in 1986 (80.1 ± 8.9 vs. 75.4 ± 6.7 years, p < 0.0001). The main increase was in the percentage of patients over 85 years: 11.39% in 1986 versus 26.98% in 2006. There was no significant difference between the two groups as regards gender or type of CNV. Conclusions: In our clinical setting, the average age of patients with newly diagnosed exudative AMD increased significantly between 1986 and 2006. The fact that in the present series more than 1 out of 4 patients was over 85 may have a significant impact on the potential side effects of currently available treatments of exudative AMD.

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The US Twin Study of Age-Related Macular Degeneration

Cited by 379 publications

References 56 publications

Genetic Factors Associated with Age-Related Macular Degeneration

Genetic Factors Associated with Age-Related Macular Degeneration

Mapping rare, deleterious mutations in Factor H: Association with early onset, drusen burden, and lower antigenic levels in familial AMD

Age at Occurrence of Exudative Age-Related Macular Degeneration in a Clinical Setting: Difference between 1986 and 2006

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