ClinSeq

临床测序

• 批准号: 8350014
• 负责人: Leslie Biesecker
• 金额: $ 122.94万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8350014
• 关键词: Address; Atherosclerosis; Biomedical Research; Blood Pressure; Blood specimen; Cardiovascular system; Clinical; Clinical Research; Consent; Coupling; DNA; DNA Sequence; Data; Data Set; Development; Family; Generations; Genetic Counseling; Genomics; Genotype; Health behavior; Individual; Lipids; Medical; Medical Genetics; Participant; Persons; Phenotype; Production; Recording of previous events; Research; Research Infrastructure; Sampling; Technical Expertise; Testing; United States National Institutes of Health; Variant; cohort; coronary artery calcification; design; disease phenotype; exome; falls; peripheral blood; prospective; research clinical testing; sample collection; trait

The specific aims of ClinSeq include: 1. Pilot the development of a robust infrastructure for the generation and use of LSMS data from subjects in a clinical research setting. This will involve the coupling of the NISC production-oriented DNA sequencing group with the NIH Clinical Research Center. We will establish technical expertise for generating, handling, and interpreting LSMS clinical research data. 2. Use LSMS data to address biomedical research questions. For example: (l) testing associations of genomic variants with quantitative traits identified in subjects (such as atherosclerosis and lipid levels); (2) using LSMS data to identify subsets of subjects from the prospective cohort, who can then be invited to return to the NIH Clinical Research Center for additional phenotyping and in-depth study: and (3) using this cohort for replication studies of associations of genomic variants and phenotypes. A cohort of 1,000 individuals will be evaluated at the NIH Clinical Research Center for a set of cardiovascular phenotypic features, including, but not limited to, coronary artery calcification, lipid profiles, and blood pressure. Participants will be selected to fall within a spectrum of coronary artery calcification from normal to disease phenotype. Participants will undergo a clinical evaluation, targeted clinical tests, and blood sample collection for genomic analysis and they will provide baseline information about pertinent health behavior and a family history. Exome sequencing of peripheral blood DNA will be performed on all samples and has been completed in >600 subjects to date. Importantly, ClinSeq subjects will be consented for return of results (both research and clinical results) and for re-contact for iterative phenotyping. ClinSeq was designed in a way that will provide the long-term potential for pursuing many different clinical projects. We propose to select subsets of subjects from the ClinSeq dataset, identified by their genomic attributes, explore their phenotypic manifestations, as a new path to understanding genotype-phenotype relationships.

Clinseq的具体目的包括： 1。促进了在临床研究环境中从受试者中生成和使用LSMS数据的强大基础设施的开发。这将涉及将NISC生产的DNA测序组与NIH临床研究中心耦合。 我们将建立技术专长，以生成，处理和解释LSMS临床研究数据。 2。使用LSMS数据来解决生物医学研究问题。例如：（l）测试基因组变体与受试者（例如动脉粥样硬化和脂质水平）中鉴定的定量特征的关联； （2）使用LSMS数据来识别前瞻性队列的受试者的子集，然后邀请他们返回NIH临床研究中心进行其他表型和深入研究：和（3）使用此组进行基因组变体和表型关联的复制研究。 将在NIH临床研究中心评估1,000名个人的队列，以了解一组心血管表型特征，包括但不限于冠状动脉钙化，脂质谱和血压。参与者将被选为从正常到疾病表型的冠状动脉钙化范围内。参与者将接受临床评估，有针对性的临床测试以及用于基因组分析的血液样本收集，他们将提供有关相关健康行为和家族史的基线信息。外周血DNA的外显子组测序将对所有样品进行，并已在迄今为止> 600名受试者中完成。重要的是，将同意Clinseq受试者的结果（研究和临床结果）以及重新接触迭代表型。 Clinseq的设计方式将为追求许多不同的临床项目提供长期潜力。我们建议从Clinseq数据集中选择受试者的子集，并通过其基因组属性确定，探索其表型表现，作为理解基因型 - 表型关系的新途径。