Heritability of retinal drusen in the Copenhagen Twin Cohort Eye Study

Abstract

Purpose To study age‐ and sex‐adjusted heritability of small hard drusen and early age‐related macular degeneration (AMD) in a population‐based twin cohort. Methods This was a single‐centre, cross‐sectional, classical twin study with ophthalmic examination including refraction, biometry, best‐corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location. Results The study enrolled 176 same‐sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes ≥20 small hard macular drusen (largest diameter < 63 μm), ≥20 small hard extramacular drusen, intermediate drusen (63–125 μm) anywhere, and large drusen (>125 μm) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5–82.9], 69.1% [62.3–75.9], 30.1% [4.1–56.1], and 65.6% [26.4–100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of ≥20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier. Conclusion Numerous (≥20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age.

Heritability and Risk Factors of Incident Small and Large Drusen in the Copenhagen Twin Cohort Eye Study: A 20-Year Follow-Up

“…The emergence of smoking as an identifiable risk factor between the baseline and follow-up visits in our cohort supports that AMD risk factors include exposures that are present late in life [15]. This agrees with the observation that the heritability of small hard drusen decreases with increasing age [32].…”

Age‐related macular degeneration discordance in monozygotic twin pairs

“…Different drusen phenotypes have shown heritability estimates ranging from 30.1 up to 81.0% Abbreviations: AMD, Age-related macular degeneration; AREDS, Age-Related Eye Disease Study. (Belmouhand et 2022;Hammond et al, 2002;Seddon et al, 2005). Macular pigmentary changes (increased pigmentation/depigmentation) have shown a lower heritability of 35%-46% (Hammond et al, 2002, Seddon et al, 2005.…”

“…AMD phenotypical features have shown high degrees of heritability in previous classic twin studies. Different drusen phenotypes have shown heritability estimates ranging from 30.1 up to 81.0% (Belmouhand et al., 2022; Hammond et al., 2002; Seddon et al., 2005). Macular pigmentary changes (increased pigmentation/depigmentation) have shown a lower heritability of 35%–46% (Hammond et al., 2002, Seddon et al., 2005).…”