Investigating Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of visual impairment in the United States. Available evidence suggests that AMD is a complex disorder with a significant genetic component as well as potential environmental influences. In this study we propose to examine 3,000 members, ages 50 and older, of the Old Order Amish community in the Lancaster and Franklin counties area in Pennsylvania. We plan to detail the epidemiology of AMD in this population isolate in attempt to elucidate genetic factors which may confer susceptibility and predispose some Amish individuals and their families to develop AMD. All study participants agreeing to enroll and providing informed consent will undergo a complete, dilated eye examination during which digital stereo images of the macula and optic disc regions will be acquired. Study participants will also be asked to complete a brief questionnaire inquiring about personal exposures related to occupation, sunlight, and smoking. AMD will be determined by an independent reading of the digital fundus photographs by the University of Wisconsin Fundus Photography Reading Center according to the AREDS AMD classification scheme. We will employ standard statistical genetics methods of parametric and non-parametric linkage analysis, association analysis, and transmission disequilibrium tests, with allowances for environmental (i.e. non-genetic) factors to determine if we can identify any candidate regions or candidate genes that predispose Amish individuals to an increased risk of AMD. Ultimately, we hope to follow up any regions that show suggestive evidence of linkage on the genome-wide scan with fine mapping in those regions, leading to eventual cloning and sequencing of a gene or genes.