GENETIC PREDISPOSITION TO DRUSEN FORMATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 老年性黄斑病变(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进展为老年性黄斑变性(AMD)是美国老年人口失明的主要原因。大约有170万40岁或40岁以上的美国人处于晚期，730万人处于AMD的早期阶段。尽管对AMD进行了广泛的研究，但玻璃体形成在AMD发病机制中的作用仍不清楚。这一过程中的一个假设是，玻璃疱疹代表疾病自然历史的早期阶段，其他基因是疾病发展到渗出期或新生绒毛膜阶段所必需的。为了测试促进玻璃体形成的基因是否独立于AMD的发病机制，我们对两种不同的表型进行了基因组扫描：最大玻璃体大小和严重玻璃体类型。我们使用了来自两个不同队列的数据--海狸水坝眼科研究(BDES)和家庭年龄相关性黄斑病变研究(FARMS)--来验证这一假设。BDES从早到晚都有ARM严重程度的所有家系，之前已经对ARM的遗传学进行了分析。农场数据集包括通过患有严重AMD的先证者确定的家庭，还进行了AMD的基因组扫描。结果表明，APOE效应可能在ARM发展为AMD的早期参与，因此可能无法通过标准的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.