Genomic Architecture of Common Disease in Diverse Populations

 描述(由申请人提供)：常见、复杂的疾病构成了人类健康的主要负担。罕见的基因变异是疾病风险的重要组成部分，全面了解基因结构将需要对数十万人--甚至数百万人--进行研究。研究设计，包括种族多样性和家系，以及利用接近基因水平的表型将是早期成功的关键。通过三个发现项目，我们将在表型良好的个人中产生50,000个全基因组序列，以研究心血管系统、骨骼和新陈代谢的障碍。这些项目将利用Illumina HiSeq X仪器以及贝勒医学院人类基因组测序中心的世界级分析和信息学管道。研究非编码变异，包括长阅读单倍型和结构变异的方法将是 从头到尾都给予特别的关注。在发现项目之后，将进行更大数量的重复研究，病例队列策略将汇总这些数据，作为通过大型医疗保健网络招募患者的综合试验的前奏。这些预期的收藏是实现精准医学的第一步。

 DESCRIPTION (provided by applicant): Common, complex diseases constitute a major human heath burden. Rare genetic variants are an important component of disease risk and a full understanding of genetic architecture will require studies of hundreds of thousands - perhaps millions - of individuals. Study design, including ethnic diversity and pedigrees, and leveraging phenotypes proximal to the gene level will be critical for early success. Across three Discovery Projects, we will generate 50,000 whole genome sequences in well-phenotyped individuals to study disorders of the cardiovascular system, bone and metabolism. These projects will utilize Illumina HiSeq X instruments and the world-class analysis and informatics pipelines at Baylor College of Medicine's Human Genome Sequencing Center. Methods for investigating noncoding variation, including long-read haplotypes and structural variation, will be given particular attention throughout. The discovery projects will be followed by replication studies in even larger numbers, and a case-cohort strategy will aggregate these data as a prelude to a comprehensive experiment based on recruitment of patients via large health care networks. These prospective collections are a first step toward realizing precision medicine.