GENETIC PREDISPOSITION TO DRUSEN FORMATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 视网膜相关性黄斑病变（ARM）是一种复杂的退行性眼病，主要影响眼睛的黄斑区域。 从ARM进展为年龄相关性黄斑变性（AMD）是美国老年人群失明的主要原因。 大约170万40岁或以上的美国人患有晚期AMD，730万人患有早期AMD。 尽管对AMD进行了广泛的研究，但玻璃疣形成对AMD发病机制的影响仍然未知。 这个过程中的一个假设是玻璃疣代表疾病自然史的早期阶段，并且其他基因对于疾病进展到渗出或新生血管阶段是必需的。 为了测试促进玻璃疣形成的基因是否独立于AMD发病机制，我们对两种不同的表型进行了基因组扫描：最大玻璃疣大小和严重玻璃疣类型。 我们使用来自两个不同队列的数据，比弗坝眼科研究（BDES）和家庭年龄相关性黄斑病变研究（FARMS），以检验这一假设。 BDES具有从早期到晚期的所有等级的ARM严重性的家族，并且先前已经分析了ARM. FARMS数据集包括通过患有严重AMD的先证者确定的家族，并且还进行了AMD的基因组扫描。 结果表明，APOE效应可能在ARM向AMD进展的早期介导，因此可能无法通过标准基因组扫描检测到更严重的疾病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related maculopathy (ARM) is a complex degenerative eye disorder that primarily affects the macular region of the eye. Progression from ARM to age-related macular degeneration (AMD) is the main cause of blindness in the elderly population in the United States. Approximately 1.7 million American 40 years of age or older have the advanced stages and 7.3 million show the earlier stages of AMD. Despite extensive research on AMD, the effect of drusen formation on AMD pathogenesis remains unknown. One assumption in this process is that drusen represent an early stage in the natural history of disease and that other genes are necessary for the progression to exudative or neovasuclar stages of the disease. To test whether genes that promote drusen formation are independent of AMD pathogenesis, we conducted genome scans on two separate phenotypes: maximum drusen size and severe drusen type. We used data from two different cohorts, the Beaver Dam Eye Study (BDES) and the Family Age Related Maculopathy Study (FARMS), to test this hypothesis. The BDES has families with all grades of ARM severity, from early to late, and has previously been analyzed for the genetics of ARM. The FARMS data set includes families ascertained through probands with severe AMD, and a genome scan for AMD has also been conducted. The results showed that APOE effects may be mediated early in the progression of ARM to AMD and thus may not be detected by standard genome scans for more severe disease.