Etiologic Studies of Age-Related Macular Degeneration

描述（由申请人提供）：我们假设潜在的易感基因对年龄相关性黄斑变性（AMD）的发展至关重要，并且它们很可能与环境因素相互作用，引发该疾病的发展和进展。我们提出了一种多管齐下的方法来鉴定年龄相关性黄斑变性（AMD）的易感基因。在最初的资助期间，我们开发了一个大型遗传AMD数据库，包括大家庭和有患病兄弟姐妹对的多重家庭，并确定了几个遗传联系领域。在下一个拨款期间，我们提出了一个多管齐下的方法来建立这个数据库，目标是找到与AMD易感性相关的基因或基因。我们将使用基于家庭和基于人群的病例对照关联研究，并结合扩展的全基因组兄弟姐妹对研究。高优先位置或功能性AMD候选基因座中的单核苷酸多态性将用于关联研究，并进行连锁不平衡和传递不平衡测试。利用扩大的全基因组扫描的定量和定性性状进行兄弟姐妹对连锁分析。我们将收集家族病史和风险因素数据，并对AMD的这些风险因素进行研究。这些数据将为分析环境因素的影响提供重要信息，因为确定了与该疾病有关的特定遗传因素的信息。黄斑变性是全球老年人不可逆失明的主要原因，本研究将为黄斑变性的病因提供重要的新信息，从而制定预防或治疗措施。

DESCRIPTION (provided by applicant): We hypothesize that underlying susceptibility gene (s) are critical to the development of age-related macular degeneration (AMD) and that they most likely interact with environmental factors to trigger the development and progression of this disease. We propose a multi-pronged approach to the identification of susceptibility gene(s) for age-related macular degeneration (AMD). During the initial grant period we developed a large genetic AMD database including large families and multiplex families with affected sib-pairs, and have identified several areas of genetic linkage to pursue. During the next grant period, we propose a multipronged approach to build upon this database, with the goal of finding the gene or genes associated with AMD susceptibility. We will use family-based and population-based case-control association studies, combined with an expanded genome-wide sib-pair study for this project. Single nucleotide polymorphisms in high priority positional or functional AMD candidate loci will be genotyped for the association studies and linkage disequilibrium and transmission disequilibrium tests will be performed. Sib-pair linkage analysis using both quantitative and qualitative traits on the expanded genome-wide scan will be completed. We will collect family history and risk factor data and conduct studies examining these risk factors for AMD. These data will provide important information to analyze the influence of environmental factors as information about specific genetic factors involved in the disease is identified. This study should provide important new information about the etiology of AMD which is the leading cause of irreversible blindness among elderly individuals worldwide, so that preventative or treatment measures can be developed.