Functional Genomics of Complex Vascular Disease

描述（由申请人提供）：德克萨斯大学西南医学中心（Core）心脏病学部寻求扩大其在复杂血管疾病方面的研究。为此，我们正在积极从NHLBI招募一名新的独立调查员Santhi Ganesh医学博士，以促进我们在这一领域的发展。自2003年人类基因组计划和2005年国际HapMap计划完成以来，旨在了解复杂人类疾病的遗传技术迅速发展，包括用于病例对照的高密度单核苷酸多态性（SNP）基因分型和基于人群的关联检测和测序。这些遗传方法通过全基因组关联研究（GWAS）的应用，导致了与心血管疾病前所未有的新关联，报告了200多个此类关联。目前，一个主要的知识缺口是缺乏对这些关联在常见变异的预测效用和遗传关联的功能相关性方面的影响的理解。展望未来，我们建议在Ganesh博士的指导下进行调查，以破译与人类血管疾病相关的遗传位点变异的生物学后果。我们已经确定了一个由合作者和导师组成的核心小组，他们将与Ganesh博士一起启动她的独立研究项目。此外，我们的核心部门已经对Ganesh博士的成功做出了重大承诺，包括在这里提议的两年资助期之后支持她的计划。总之，我们提出了一个精心策划的调查和职业发展计划，该计划既适合NIl的具体需求，也适合我们部门/核心内新的多学科研究项目的出现。

DESCRIPTION (provided by applicant): The Division of Cardiology at the University of Texas Southwestern Medical Center (Core) seeks to expand its research in complex vascular disease. To this end, we are actively recruiting a newly independent investigator (NIl), Santhi Ganesh, MD, from the NHLBI to facilitate our growth in this area. Since the completion of the Human Genome Project in 2003 and the International HapMap Project in -2005, there has been a rapid expansion in genetic technologies aimed to understand complex-human diseases, including high-density single nucleotide polymorphism (SNP) genotyping for case-control and population-based association testing and sequencing. The application of these genetic methods through genome-wide association studies (GWAS) has led to an unprecedented number of novel associations with cardiovascular diseases, with over 200 such associations reported. Currently, a major knowledge gap is lack of understanding of the impact of these associations in terms of the predictive utility of common variants and in terms of the functional relevance of genetic associations. Moving forward, we propose to pursue investigation under the direction of Dr. Ganesh to decipher the biologic consequences of variation in genetic loci associated with human vascular disease. We have identified a core group of collaborators and mentors who will work with Dr. Ganesh in the launch of her program of independent research. Further, our Division/Core has made a major commitment to Dr. Ganesh's success, including plans to support her beyond the two-year funding period proposed here. In summary, we propose a well orchestrated plan of investigation and career development which is at once tailored to the NIl's specific needs and to the emergence of new, multidisciplinary programs of research within our Division/Core.