Center for Common Disease Genetics

 描述(由申请人提供)：基于我们25年来在全面基因组研究方面的跟踪记录，并解决NHGRI对此项RFA的目标，我们建议创建、应用和测试一种强大、可靠和通用的策略，用于“全面”识别对任何常见疾病有重大贡献的风险和保护性变异。为此，我们将：*创建一个常见疾病联盟(CDC)，将拥有深厚临床和遗传专业知识的研究人员以及110万个特征良好的样本(病例和对照)聚集在一起，这些样本分布在不同的人群中，包括欧洲人、非裔美国人、拉美裔和亚洲人。疾控中心将在三个主要项目下进行基因研究，这些项目涉及：(1)五种全身性疾病--早发性冠状动脉疾病、2型糖尿病、炎症性肠病、房颤和中风；(2)三种严重的神经疾病--自闭症、精神分裂症和癫痫；(3)两个在基因研究方面具有特殊优势的国家--芬兰和爱沙尼亚。通过这三个项目，疾控中心将探索一系列的研究设计、种群遗传策略、遗传结构和不同的种群。*对疾控中心的45万个样本进行测序，利用布罗德研究所的基因组学平台的专业知识来生成高质量的数据，并降低测序成本。通过在我们的初步研究中应用最先进的方法和开发新的方法来增加检测关联的能力，分析序列数据以阐明疾病的遗传基础。创建、传播和共享数据、工具和资源，使科学界能够访问和分析来自疾控中心和其他来源的基因研究。

 DESCRIPTION (provided by applicant): Building on our 25-year track record in comprehensive genomic studies and addressing NHGRI's goal for this RFA, we propose to create, apply and test a powerful, reliable and general strategy for "comprehensive" identification of risk and protective variants that contribute significantly to any common disease of interest. Toward this end, we will: * Create a Common Disease Consortium (CDC) that brings together a collaborative network of investigators with deep clinical and genetic expertise and >1.1 million well-characterized samples (cases and controls) across diverse populations, including Europeans, African Americans, Hispanics and Asians. The CDC will undertake genetic studies under three major projects related to: (1) Five systemic diseases - early-onset coronary artery disease, type 2 diabetes, inflammatory bowel disease, atrial fibrillation, and stroke; (2) Three severe neurological disorders - autism, schizophrenia and epilepsy; and (3) Two countries with special advantages for genetic studies - Finland and Estonia. Through these three projects, the CDC will explore a range of study designs, population-genetic strategies, genetic architectures, and diverse populations. * Sequence 450,000 samples from the CDC, using the expertise of the Broad Institute's genomics platform to generate high quality data and to drive down sequencing costs. Analyze the sequence data to elucidate the genetic basis of the diseases, by applying state- of-the-art methods from in our preliminary studies and developing new methods to increase power to detect association. Create, disseminate and share data, tools, and resources, to enable the scientific community to access and analyze genetic studies from the CDC and other sources.