Framingham Cohort

**Startup of Framingham Heart Study.** Cardiovascular disease (CVD) is the leading cause of death and serious illness in the United States. In 1948, the Framingham Heart Study (FHS) -- under the direction of the National Heart Institute (now known as the National Heart, Lung, and Blood Institute, NHLBI) -- embarked on a novel and ambitious project in health research. At the time, little was known about the general causes of heart disease and stroke, but the death rates for CVD had been increasing steadily since the beginning of the century and had become an American epidemic.

The objective of the FHS was to identify the common factors or characteristics that contribute to CVD by following its development over a long period of time in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke.

**Design of Framingham Heart Study.** In 1948, the researchers recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts, and began the first round of extensive physical examinations and lifestyle interviews that they would later analyze for common patterns related to CVD development. Since 1948, the subjects have returned to the study every two years for an examination consisting of a detailed medical history, physical examination, and laboratory tests, and in 1971, the study enrolled a second-generation cohort -- 5,124 of the original participants' adult children and their spouses -- to participate in similar examinations. The second examination of the Offspring cohort occurred eight years after the first examination, and subsequent examinations have occurred approximately every four years thereafter. In April 2002 the Study entered a new phase: the enrollment of a third generation of participants, the grandchildren of the original cohort. The first examination of the Third Generation Study was completed in July 2005 and involved 4,095 participants. Thus, the FHS has evolved into a prospective, community-based, three generation family study. The FHS is a joint project of the National Heart, Lung and Blood Institute and Boston University.

**Research Areas in the Framingham Heart Study.** Over the years, careful monitoring of the FHS population has led to the identification of the major CVD risk factors -- high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity -- as well as a great deal of valuable information on the effects of related factors such as blood triglyceride and HDL cholesterol levels, age, gender, and psychosocial issues. Risk factors have been identified for the major components of CVD, including coronary heart disease, stroke, intermittent claudication, and heart failure. It is also clear from research in the FHS and other studies that substantial subclinical vascular disease occurs in the blood vessels, heart and brain that precedes clinical CVD. With recent advances in technology, the FHS has enhanced its research capabilities and capitalized on its inherent resources by the conduct of high resolution imaging to detect and quantify subclinical vascular disease in the major blood vessels, heart and brain. These studies have included ultrasound studies of the heart (echocardiography) and carotid arteries, computed tomography studies of the heart and aorta, and magnetic resonance imaging studies of the brain, heart, and aorta. Although the Framingham cohort is primarily white, the importance of the major CVD risk factors identified in this group have been shown in other studies to apply almost universally among racial and ethnic groups, even though the patterns of distribution may vary from group to group. In the past half century, the Study has produced approximately 1,200 articles in leading medical journals. The concept of CVD risk factors has become an integral part of the modern medical curriculum and has led to the development of effective treatment and preventive strategies in clinical practice.

In addition to research studies focused on risk factors, subclinical CVD and clinically apparent CVD, Framingham investigators have also collaborated with leading researchers from around the country and throughout the world on projects involving some of the major chronic illnesses in men and women, including dementia, osteoporosis and arthritis, nutritional deficiencies, eye diseases, hearing disorders, and chronic obstructive lung diseases.

**Genetic Research in the Framingham Heart Study.** While pursuing the Study's established research goals, the NHLBI and the Framingham investigators has expanded its research mission into the study of genetic factors underlying CVD and other disorders. Over the past two decades, DNA has been collected from blood samples and from immortalized cell lines obtained from Original Cohort participants, members of the Offspring Cohort and the Third Generation Cohort. Several large-scale genotyping projects have been conducted in the past decade. Genome-wide linkage analysis has been conducted using genotypes of approximately 400 microsatellite markers that have been completed in over 9,300 subjects in all three generations. Analyses using microsatellite markers completed in the original cohort and offspring cohorts have resulted in over 100 publications, including many publications from the Genetics Analysis Workshop 13. Several other recent collaborative projects have completed thousands of SNP genotypes for candidate gene regions in subsets of FHS subjects with available DNA. These projects include the Cardiogenomics Program of the NHLBI's Programs for Genomics Applications, the genotyping of ~3000 SNPs in inflammation genes, and the completion of a genome-wide scan of 100,000 SNPs using the Affymetrix 100K Genechip.

**Framingham Cohort Phenotype Data.** The phenotype database contains a vast array of phenotype information available in all three generations. These will include the quantitative measures of the major risk factors such as systolic blood pressure, total and HDL cholesterol, fasting glucose, and cigarette use, as well as anthropomorphic measures such as body mass index, biomarkers such as fibrinogen and CRP, and electrocardiography measures such as the QT interval. Many of these measures have been collected repeatedly in the original and offspring cohorts. Also included in the SHARe database will be an array of recently collected biomarkers, subclinical disease imaging measures, clinical CVD outcomes as well as an array of ancillary studies. The phenotype data is located here in the top-level study phs000007 Framingham Cohort. To view the phenotype variables collected from the Framingham Cohort, please click on the "Variables" tab above.

**The Framingham Cohort is utilized in the following dbGaP substudies.** To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000007 Framingham Cohort.
- [phs000342](./study.cgi?study_id=phs000342) Framingham SHARe - [phs000282](./study.cgi?study_id=phs000282) Framingham CARe - [phs000363](./study.cgi?study_id=phs000363) Framingham SABRe - [phs000307](./study.cgi?study_id=phs000307) Framingham Medical Resequencing - [phs000401](./study.cgi?study_id=phs000401) Framingham ESP Heart-GO - [phs000651](./study.cgi?study_id=phs000651) Framingham CHARGE-S - [phs000724](./study.cgi?study_id=phs000724) Framingham DNA Methylation - [phs001610](./study.cgi?study_id=phs001610) Framingham T2D-GENES - [phs002558](./study.cgi?study_id=phs002558) Framingham ADSP - [phs002559](./study.cgi?study_id=phs002559) Framingham BRIDGET - [phs002560](./study.cgi?study_id=phs002560) Framingham Cholesterol - [phs002611](./study.cgi?study_id=phs002611) Framingham Post-Mortem Brain Tissue

The unflagging commitment of the research participants in the NHLBI FHS has made more than a half century of research success possible. For decades, the FHS has made its data and DNA widely available to qualified investigators throughout the world through the Limited Access Datasets and the FHS DNA Committee, and the SHARe database will continue that tradition by allowing access to qualified investigators who agree to the requirements of data access. With the SHARe database, we continue with an ambitious research agenda and look forward to new discoveries in the decades to come.

**弗雷明汉心脏研究（Framingham Heart Study, FHS）的启动**
心血管疾病（Cardiovascular Disease, CVD）是美国致死与致残的首要病因。1948年，弗雷明汉心脏研究（Framingham Heart Study, FHS）在美国国家心脏研究所（现更名为美国国家心肺血液研究所，National Heart, Lung, and Blood Institute, NHLBI）的主导下，启动了一项具有开创性与前瞻性的健康研究项目。彼时，学界对心脏病与中风的普遍致病机制尚所知甚少，但自20世纪初以来，CVD的死亡率持续攀升，已演变为美国范围内的流行性公共卫生问题。
本研究的核心目标为：通过长期追踪一大群尚未出现显性CVD症状、未发生过心肌梗死或中风的受试者的健康轨迹，识别与CVD发生发展相关的常见风险因素与特征。

**弗雷明汉心脏研究的研究设计**
1948年，研究人员从马萨诸塞州弗雷明汉镇招募了5209名年龄在30至62岁之间的男女受试者，启动了首轮全面体格检查与生活方式访谈，后续将通过分析这些数据探寻与CVD发生相关的共性规律。自1948年起，受试者每两年返回研究中心接受一次检查，检查内容涵盖详细病史采集、体格检查与实验室检测。1971年，研究新增了第二代队列：5124名原队列受试者的成年子女及其配偶，参与类似的随访检查。子代队列的第二次检查于首次检查后8年开展，此后的随访检查大致每四年进行一次。2002年4月，本研究进入全新阶段：招募第三代受试者，即原队列受试者的孙辈。第三代研究的首轮检查于2005年7月完成，共纳入4095名受试者。至此，弗雷明汉心脏研究已发展为一项前瞻性、以社区为基础的三代家庭队列研究。本研究由美国国家心肺血液研究所与波士顿大学联合开展。

**弗雷明汉心脏研究的研究方向**
多年来，通过对弗雷明汉研究队列的精细化监测，研究团队已明确了CVD的主要风险因素——高血压、高胆固醇血症、吸烟、肥胖、糖尿病与体力活动不足，同时积累了大量关于血脂甘油三酯、高密度脂蛋白（HDL）胆固醇水平、年龄、性别与社会心理因素等相关因素影响的珍贵研究数据。研究团队还明确了CVD主要亚型的风险因素，包括冠心病、中风、间歇性跛行与心力衰竭。此外，基于弗雷明汉研究与其他研究的结果可知，在临床CVD发病前，血管、心脏与大脑中已存在显著的亚临床血管病变。随着近年来技术进步，弗雷明汉研究依托其固有资源优势，通过高分辨率成像技术检测并量化主要血管、心脏与大脑中的亚临床血管病变，相关研究包括心脏（超声心动图）与颈动脉超声检查、心脏与主动脉计算机断层扫描（CT），以及大脑、心脏与主动脉磁共振成像（MRI）检查。尽管弗雷明汉队列以白人为主，但其他研究已证实，本研究中识别的主要CVD风险因素几乎适用于所有种族与民族群体，仅风险因素的分布模式存在群体差异。在过去半个世纪中，本研究已在顶尖医学期刊发表约1200篇学术论文。CVD风险因素的相关概念已成为现代医学教育的核心内容之一，并推动了临床实践中有效治疗与预防策略的发展。
除针对CVD风险因素、亚临床CVD与临床显性CVD的研究外，弗雷明汉研究团队还与全球各地的顶尖研究者合作，开展了针对男女群体主要慢性疾病的相关研究，包括痴呆、骨质疏松与关节炎、营养缺乏症、眼部疾病、听力障碍与慢性阻塞性肺疾病等。

**弗雷明汉心脏研究的遗传学研究**
在推进既定研究目标的同时，美国国家心肺血液研究所与弗雷明汉研究团队还将研究范畴拓展至CVD及其他疾病的遗传致病机制研究。过去二十年间，研究团队从原队列、子代队列与第三代队列的受试者的血液样本及永生化细胞系中提取了DNA。近十年来，已开展多项大规模基因分型项目。研究团队利用约400个微卫星标记的基因型数据，对三代队列中超过9300名受试者进行了全基因组连锁分析。基于原队列与子代队列的微卫星标记分析已发表超过100篇学术论文，其中包括第13届遗传学分析研讨会（Genetics Analysis Workshop 13）的多篇成果。近期的多项合作项目还对携带可用DNA的弗雷明汉研究亚队列受试者的候选基因区域完成了数千个单核苷酸多态性（Single Nucleotide Polymorphism, SNP）的基因分型工作，这些项目包括美国国家心肺血液研究所基因组应用项目旗下的心脏基因组学项目、炎症基因中约3000个SNP的基因分型，以及使用昂飞（Affymetrix）100K基因芯片完成的10万个SNP的全基因组扫描。

**弗雷明汉队列表型数据**
本研究的表型数据库涵盖了三代队列的海量表型信息，包括主要风险因素的定量检测指标，如收缩压、总胆固醇与高密度脂蛋白胆固醇水平、空腹血糖与吸烟情况；同时包含人体测量学指标（如体重指数（Body Mass Index, BMI））、生物标志物（如纤维蛋白原与C反应蛋白（C-reactive Protein, CRP））以及心电图（Electrocardiography, ECG）指标（如QT间期）等。原队列与子代队列的多项指标均已进行了多次重复采集。SHARe数据库还将纳入一系列新近采集的生物标志物、亚临床疾病成像检测数据、临床CVD转归数据以及多项辅助研究数据。弗雷明汉队列的表型数据存储于顶层研究phs000007 Framingham Cohort中。若需查看弗雷明汉队列采集的表型变量，请点击上方的"Variables"标签。

**弗雷明汉队列应用于以下dbGaP（Database of Genotypes and Phenotypes, dbGaP）子研究**
若需查看这些子研究中采集的基因型数据、分析结果、表达数据、其他分子数据及衍生变量，请点击下方列出的子研究，或访问顶层研究页面phs000007 Framingham Cohort的"Substudies"板块。
- [phs000342](./study.cgi?study_id=phs000342) 弗雷明汉SHARe研究
- [phs000282](./study.cgi?study_id=phs000282) 弗雷明汉CARe研究
- [phs000363](./study.cgi?study_id=phs000363) 弗雷明汉SABRe研究
- [phs000307](./study.cgi?study_id=phs000307) 弗雷明汉医学重测序研究
- [phs000401](./study.cgi?study_id=phs000401) 弗雷明汉ESP Heart-GO研究
- [phs000651](./study.cgi?study_id=phs000651) 弗雷明汉CHARGE-S研究
- [phs000724](./study.cgi?study_id=phs000724) 弗雷明汉DNA甲基化研究
- [phs001610](./study.cgi?study_id=phs001610) 弗雷明汉T2D-GENES研究
- [phs002558](./study.cgi?study_id=phs002558) 弗雷明汉ADSP研究
- [phs002559](./study.cgi?study_id=phs002559) 弗雷明汉BRIDGET研究
- [phs002560](./study.cgi?study_id=phs002560) 弗雷明汉胆固醇研究
- [phs002611](./study.cgi?study_id=phs002611) 弗雷明汉死后脑组织研究

美国国家心肺血液研究所弗雷明汉心脏研究的受试者们始终不渝的参与与奉献，促成了半个多世纪以来的研究成就。数十年来，弗雷明汉研究通过受限访问数据集（Limited Access Datasets）与弗雷明汉DNA委员会，向全球符合资质的研究人员开放其数据与DNA样本资源。SHARe数据库将延续这一传统，允许符合数据访问要求的合格研究人员使用相关数据。依托SHARe数据库，本研究将继续推进前瞻性的研究计划，并期待在未来数十年中取得更多全新的科研发现。