Advancing genomics through the AMD Genomics Consortium

老年性黄斑变性(AMD)是导致老年人失明的主要原因之一。它有一个 对患者的独立性、生活质量和医疗费用产生重大影响 照顾者和家庭成员的额外社会成本是无法估量的。有很大的变异性，在 AMD的表型和初步治疗，反复向眼内注射抗血管内皮生长因子抗体 受严重影响，只对一小部分人有效。从而更好地理解潜在的 AMD的病因需要帮助指导开发更普遍和有效的治疗方法和潜力 AMD的预防措施。 AMD受基因组变异的影响很大。在这项建议的最初资助期内，我们 支持国际AMD基因组学联盟(IAMDGC)的发展，该联盟汇集了 来自世界各地的26个研究小组。IAMDGC已将已知的基因组座位从12个增加到52个 并成功地进行了一项新的更大规模的基因分型研究，重点是使用高密度的 含有外显子的全基因组SNP芯片。这一合作努力还催生了许多其他 有趣的研究途径，我们现在需要通过高度更新来更详细地探索 成功的项目。虽然目前超过50,000个样本的基因分型数据集还有很多有待挖掘的地方， 扩大现有样本是必要的，特别是对家庭和少数群体样本，如果我们 是为了实现我们宣布的完全定义AMD基因结构的目标。要解决这些问题 悬而未决的问题我们提出了四个具体目标：1)用更多的数据集扩大IAMDGC资源 和扩展当前的数据集，重点放在家庭数据和多样化的遗传祖先上；2)扩展 临床诊断措施的范围(例如眼底照片、OCT测量)、生物标志物、合并症和 与样本相关的协变量数据；3)使用分析中心基础设施来执行详细的 对这些数据的分析；以及4)为IAMDGC的后勤和管理提供支持。

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly. It has a significant impact on the independence, quality of life, and healthcare costs for those afflicted and the additional social cost on caregivers and family members is incalculable. There is substantial variability in the AMD phenotype and the primary treatment, to repeatedly inject anti-VEGF antibodies into the eye of those severely affected, is effective in only a subset of individuals. Thus a better understanding of the underlying causes of AMD is needed to help guide development of more universal and effective treatments and potential preventive measures for AMD. AMD is strongly influenced by genomic variation. Through the initial funding period of this proposal, we supported the development of the International AMD Genomics Consortium (IAMDGC), which brought together 26 research groups from around the world. The IAMDGC has increased the known genomic loci from 12 to 52 and successfully performed a new and larger genotyping study focused on rarer variation using a high-density genome-wide SNP chip with exome content. This collaborative effort has also spawned numerous additional interesting avenues of research that we now need to explore in more detail through the renewal of this highly successful project. While the current genotypic dataset of over 50,000 samples has much left to be mined, expansion of the available samples, with a particular focus on families and minority samples, is necessary if we are to achieve our stated goal of completely defining the genetic architecture of AMD. To address these unresolved issues we propose four specific aims: 1) Expand the IAMDGC resource with additional datasets and expansion of current datasets, with a focus on family data and diverse genetic ancestry; 2) Expand the range of clinical diagnostic measures (e.g. fundus photos, OCT measures), biomarker, comorbidity, and covariate data associated with the samples; 3) Use an analytical hub infrastructure to perform detailed analyses of these data; and 4) Support the logistics and administration of the IAMDGC.