National Heart Lung and Blood Institute (NHLBI) GO-ESP: Heart Cohorts Component of the Exome Sequencing Project (FHS)

This substudy phs000401 Framingham ESP Heart-GO contains exome sequence data and harmonized phenotype variables, produced as part of NHLBI's GO-ESP project. Summary level phenotypes for the Framingham Cohort study participants can be viewed at the top-level study page [phs000007](./study.cgi?study_id=phs000007) Framingham Cohort. Individual level phenotype data and molecular data for all Framingham top-level study and substudies are available by requesting Authorized Access to the Framingham Cohort study [phs000007](./study.cgi?study_id=phs000007).

The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO.

HeartGO is a consortium of six well-phenotyped NHLBI cohorts: Atherosclerosis Risk in Communities (ARIC) study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS), the Jackson Heart Study (JHS), and the Multi-Ethnic Study of Atherosclerosis (MESA). Together, for the GO-ESP, these cohorts have provided DNA and phenotype datasets from a diverse cohort of individuals of African and Caucasian ancestry to be made available for use by qualified investigators in dbGaP. HeartGO investigators will conduct genotype-phenotype analyses for phenotypes related not only to heart disease but with other variables that will be contributed to dbGaP. The HeartGO dataset provides investigators with genotype-phenotype analytic opportunities for traits not only related to heart disease but also associated with ancillary variables that will be contributed to dbGaP, including disease endpoints, risk factors, biomarkers, and subclinical disease measures.

The phenotypes planned for investigation as part of the GO-ESP HeartGO project include five primary phenotypes for which initial ascertainment of samples for exome sequencing were made (early-onset myocardial infarction (EOMI), low density lipoprotein (LDL) cholesterol, body mass index/type 2 diabetes (BMI/T2D), blood pressure and ischemic stroke) and a randomly ascertained common comparison group with extensive phenotyping (deeply phenotyped reference, DPR). Additional phenotypes available on these selected samples permitted a large array of additional analyses to be performed. These secondary phenotypes account for ~80 outcomes from both qualitative and quantitative traits. Results of the proposed analyses as well as relevant replication/follow-up analyses will be reported in peer-reviewed journals.

This study phs000401 contains the Framingham Heart Study (FHS) subset of GO-ESP/Heart-GO. Additional GO-ESP data is also available via dbGaP.

本子研究phs000401 弗雷明汉ESP Heart-GO包含外显子组测序（exome sequencing）数据与标准化表型变量，该数据集作为美国国家心肺血液研究所（National Heart, Lung, and Blood Institute, NHLBI）GO-ESP项目的一部分生成。

弗雷明汉队列研究参与者的汇总级表型可在顶层研究页面[phs000007](./study.cgi?study_id=phs000007)弗雷明汉队列查看。所有弗雷明汉顶层研究及其子研究的个体级表型数据与分子数据，需通过申请获得弗雷明汉队列研究[phs000007](./study.cgi?study_id=phs000007)的授权访问权限方可获取。

美国国家心肺血液研究所“重大机遇”外显子组测序项目（Grand Opportunity Exome Sequencing Project, GO-ESP）是美国复苏法案对NHLBI投资的标志性项目，旨在识别人类基因组编码区域（外显子组，exome）中与心脏、肺及血液疾病相关的遗传变异。本项目将研究上述及其他对公共卫生与不同种族/族裔群体个体具有重大影响的相关疾病。这些数据可帮助研究者阐明疾病发病机制，助力优化疾病预防、诊断与治疗方案，同时可为针对特定人群制定个体化预防与治疗策略提供依据。此举有望催生更有效的治疗手段，并降低不良反应发生风险。GO-ESP包含五个协作模块：3个队列研究联盟——HeartGO、LungGO与WHISP，以及2个测序中心——BroadGO与SeattleGO。

HeartGO是由6个表型表征完善的NHLBI队列组成的联盟：社区动脉粥样硬化风险（Atherosclerosis Risk in Communities, ARIC）研究、青年成人冠状动脉风险发展（Coronary Artery Risk Development in Young Adults, CARDIA）研究、心血管健康（Cardiovascular Health Study, CHS）研究、弗雷明汉心脏研究（Framingham Heart Study, FHS）、杰克逊心脏研究（Jackson Heart Study, JHS）以及多民族动脉粥样硬化研究（Multi-Ethnic Study of Atherosclerosis, MESA）。针对GO-ESP项目，上述队列共提供了来自非洲裔与高加索裔多样化人群的DNA样本与表型数据集，供dbGaP中符合资质的研究者开放使用。HeartGO研究团队将开展与心脏疾病相关表型，以及将提交至dbGaP的其他变量相关的基因型-表型关联分析。HeartGO数据集为研究者提供了针对不仅与心脏疾病相关，还与将提交至dbGaP的辅助变量（包括疾病终点、危险因素、生物标志物与亚临床疾病测量指标）相关的性状开展基因型-表型分析的契机。

GO-ESP HeartGO项目计划研究的表型包括5种核心表型，针对这些表型已完成外显子组测序样本的初步招募：早发性心肌梗死（early-onset myocardial infarction, EOMI）、低密度脂蛋白（low density lipoprotein, LDL）胆固醇、体质量指数/2型糖尿病（body mass index/type 2 diabetes, BMI/T2D）、血压与缺血性脑卒中，以及一个经过广泛表型分型的随机招募普通对照人群（深度表型参考队列，deeply phenotyped reference, DPR）。上述选定样本的额外表型数据支持开展大量额外分析。这些二级表型涵盖约80个定性与定量性状结局。拟开展的分析结果及相关验证/后续分析结果将发表于同行评议期刊。

本研究phs000401包含GO-ESP/Heart-GO项目的弗雷明汉心脏研究（FHS）子集。GO-ESP的其他数据集也可通过dbGaP获取。