Icelandic Heart Association, Holtasmari 1, IS-201, Kopavogur, Iceland.
Faculty of Medicine, University of Iceland, 101, Reykjavik, Iceland.
Nat Commun. 2022 Jun 13;13(1):3401. doi: 10.1038/s41467-022-31085-x.
Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.
年龄相关性黄斑变性（AMD）是老年人视力损害最常见的原因之一，其病因复杂，目前仍了解甚少。全基因组关联研究发现了 34 个与 AMD 相关的基因组区域。然而，介导风险的基因和相关蛋白在很大程度上仍是未知的。在本研究中，我们在一项针对老年人的大型基于人群的研究中，将 4782 个人类血清蛋白水平与 AMD 的所有遗传风险位点进行了整合，揭示了许多与该疾病相关的蛋白和通路。研究还发现，血清蛋白可独立于遗传因素反映 AMD 的严重程度，并可在该人群中预测从早期 AMD 进展为晚期 AMD。两样本孟德尔随机化研究确定了几种与疾病有因果关系的蛋白，其方向与观察性估计一致。在这项工作中，我们提出了一个稳健而独特的框架，用于阐明 AMD 的病理生物学。
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