Genetic risk of age-related maculopathy - Population-based familial aggregation study

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, ie, 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.