Belmouhand Mohamed, Rothenbuehler Simon Paul, Hjelmborg Jacob B, Dabbah Sami, Bjerager Jakob, Sander Birgit Agnes, Dalgård Christine, Larsen Michael
Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital, Glostrup, Denmark.
Department of Clinical Medicine, Faculty of Healthy and Medical Science, University of Copenhagen, Copenhagen, Denmark.
Acta Ophthalmol. 2022 Dec;100(8):e1561-e1568. doi: 10.1111/aos.15136. Epub 2022 Mar 24.
To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort.
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.
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.
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.
在一项基于人群的双胞胎队列研究中，研究小而硬的玻璃膜疣及早期年龄相关性黄斑变性（AMD）经年龄和性别调整后的遗传力。
这是一项单中心、横断面的经典双胞胎研究，进行了眼科检查，包括验光、生物测量、最佳矫正视力评估、彩色和自发荧光眼底摄影以及眼底光学相干断层扫描。根据玻璃膜疣的直径和位置进行分级和分类。
该研究纳入了176对同性双胞胎，平均（标准差）年龄为58.6（9.9）岁。四种表型的患病率分别为：≥20个小而硬的黄斑玻璃膜疣（最大直径<63μm）为12.4%，≥20个小而硬的黄斑外玻璃膜疣为36.4%，任何部位的中等大小玻璃膜疣（63 - 125μm）为5.8%，任何部位的大玻璃膜疣（>125μm）为8.4%，经年龄和性别调整后的各自遗传力分别为78.2% [73.5 - 82.9]、69.1% [62.3 - 75.9]、30.1% [4.1 - 56.1]和65.6% [26.4 - 100]。年龄轨迹分析支持随着年龄增长小而硬的玻璃膜疣数量逐渐增加。≥20个小而硬的玻璃膜疣的遗传力明显低于20年前在40%重叠双胞胎队列中发现的99%。
符合干性AMD定义的大量（≥20个）小而硬的玻璃膜疣和较大玻璃膜疣具有高度遗传性。小而硬的玻璃膜疣数量随年龄增加。遗传力随年龄增长而降低表明行为和环境因素对小而硬的玻璃膜疣形成的影响随年龄增加。
