ClinSeq

ClinSeq的具体目标包括： 1. 试点开发一个强大的基础设施，用于在临床研究环境中生成和使用受试者的LSMS数据。这将涉及NISC生产导向的DNA测序组与NIH临床研究中心的耦合。 我们将建立生成、处理和解释LSMS临床研究数据的技术专长。 2. 使用LSMS数据解决生物医学研究问题。举例来说：（1）测试基因组变异与受试者中鉴定的数量性状（如动脉粥样硬化和脂质水平）的关联;（2）使用LSMS数据从前瞻性队列中鉴定受试者的子集，然后可以邀请这些受试者返回NIH临床研究中心进行额外的表型分析和深入研究;以及（3）使用该队列进行基因组变异和表型关联的复制研究。 将在NIH临床研究中心对1，000人的队列进行一组心血管表型特征的评估，包括但不限于冠状动脉钙化、血脂和血压。将选择符合从正常到疾病表型的冠状动脉钙化范围的受试者。参与者将接受临床评估，有针对性的临床测试和血液样本收集用于基因组分析，他们将提供有关相关健康行为和家族史的基线信息。将对所有样本进行外周血DNA的外显子组测序，迄今已在>600名受试者中完成。重要的是，ClinSeq受试者将同意返回结果（研究和临床结果）并重新联系以进行迭代表型分析。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子集，通过其基因组属性进行识别，探索其表型表现，作为理解基因型-表型关系的新途径。

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.