Genetic Risk of Age-related Maculopathy: Population-Based Familial Aggregation Study
Open accessAbstract
OBJECTIVE: To investigate to what extent age-related maculopathy (ARM) is genetically determined. DESIGN AND SETTING: Familial aggregation study based on probands derived from the population-based Rotterdam Study. PARTICIPANTS: First-degree relatives of 87 patients with late ARM, i.e., atrophic or neovascular macular degeneration, were compared with first-degree relatives of 135 control subjects without ARM. MAIN OUTCOME MEASURES: Presence and stage of ARM as diagnosed on fundus transparencies, odds ratio, lifetime risk, risk ratio, and population-attributable risk. RESULTS: Independent of other risk factors, the prevalence of early (odds ratio = 4.8, 95% confidence interval [CI] = 1.8-12.2) and late (odds ratio = 19.8, 95% CI = 3.1-126.0) ARM was significantly higher in relatives of patients with late ARM. The lifetime risk estimate of late ARM was 50% (95% CI = 26%-73%) for relatives of patients vs 12% (95% CI = 2%-16%) for relatives of controls (P < .001), yielding a risk ratio of 4.2 (95% CI = 2.6-6.8). Relatives of patients expressed the various features of ARM at a younger age. The population-attributable risk related to genetic factors was 23%. CONCLUSIONS: First-degree relatives of patients with late ARM developed ARM at an increased rate at a relatively young age. Our findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease.
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The contribution of genetics to AMD was documented throughout the 1990s with reports of familial aggregation, concordant phenotypes in twins, and a higher risk of disease in first-degree relatives of affected individuals.
“The contribution of genetics to AMD was carefully documented throughout the 1990s with reports of familial aggregation, concordant phenotypes in twins, and a higher risk of disease in first-degree relatives of affected individuals (69, 89, 91, 132).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [89]
Siblings of individuals with end-stage age-related macular degeneration have about a five-fold increased risk for intermediate age-related macular degeneration and a twenty-fold increased risk for advanced age-related macular degeneration.
“Klaver and colleagues47 have estimated that siblings of individuals with end-stage age-related macular degeneration have about a five-fold increased risk for intermediate age-related macular degeneration and a twenty-fold increased risk for advanced age-related macular degeneration.”
From Age-related macular degeneration (2008) · cites this paper as [47]
About 23% of advanced age-related macular degeneration can be attributed to a genetic component.
“They suggest that about 23% of advanced age-related macular degeneration can be attributed to a genetic component.”
From Age-related macular degeneration (2008) · cites this paper as [47]
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- Authors
- Klaver, C. C. W.
- Affiliations
- Erasmus MC (NL)
- Corresponding author
- Klaver, Caroline C. W.
- Venue
- Archives of Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 1998-12-01
- Volume
- 116
- Issue
- 12
- Pages
- 1646
- ISSN
- 0003-9950 (ISSN-L)
- OpenAlex
- W2144588016
- Cited by
- 323
- References
- 29
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 10 · 2016: 10 · 2015: 6 · 2014: 15 · 2013: 24 · 2012: 16
- FWCI
- 8.46
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Archives of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- age-related maculopathy, genetic susceptibility, familial aggregation, atrophic macular degeneration, neovascular age-related macular degeneration, lifetime risk, population attributable risk, first-degree relatives, Rotterdam Study
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Genetics, Population, Humans, Macular Degeneration, Male, Middle Aged, Netherlands, Nuclear Family, Risk Factors, Prevalence, Odds Ratio
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