GENETIC PREDISPOSITION TO DRUSEN FORMATION

点击翻译按钮获取中文摘要

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.