A proteogenomic signature of age-related macular degeneration in blood.
A proteogenomic signature of age-related macular degeneration in blood.
复制标题
血液中年龄相关性黄斑变性的蛋白基因组学特征
DOI：
10.1038/s41467-022-31085-x
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发表时间：
2022-06-13
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
老年性黄斑变性(AMD)是老年人视力损害最常见的原因之一，病因复杂，目前仍知之甚少。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，调节这种风险的基因和同源蛋白在很大程度上是未知的。在目前的研究中，我们在一项以老年人为基础的大型人群研究中，将4782个人类血清蛋白水平与AMD的所有遗传风险基因座整合在一起，揭示了许多与疾病相关的蛋白质和途径。血清蛋白也被发现独立于遗传因素反映AMD的严重程度，并在该人群中预测五年后从早期到晚期AMD的进展。一项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质，并与观测估计值在方向上一致。在这项工作中，我们提出了一个强大和独特的框架，以阐明AMD的病理生物学。老年性黄斑变性是老年人视力损害的常见原因，但其病因尚不完全清楚。在这里，作者使用遗传数据、血清蛋白质组学和来自冰岛大队列的AMD表型数据来发现AMD发生改变、与AMD有因果关系或标志着晚期AMD进展的蛋白质。
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. Age related macular degeneration is a common cause of visual impairment in the elderly, but the etiology is not fully understood. Here, the authors use genetic data, serum proteomics, and AMD phenotypic data from a large Icelandic cohort to discover proteins altered in, causally related to AMD or signifying progression of advanced AMD.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
11.4
作者：
Ferrington DA;Ebeling MC;Kapphahn RJ;Terluk MR;Fisher CR;Polanco JR;Roehrich H;Leary MM;Geng Z;Dutton JR;Montezuma SR
通讯作者：
Montezuma SR
影响因子：
4.2
作者：
Feher, Janos;Kovacs, Illes;Gabrieli, Corrado Balacco
通讯作者：
Gabrieli, Corrado Balacco
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R