SABRe CVD

This substudy phs000363 Framingham SABRe contains immunoassays, gene expression profiling, and microRNA data. Summary level phenotypes for the Framingham Cohort study participants can be viewed at the top-level study page 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.

Systems Approach to Biomarker Research in Cardiovascular Disease in the NHLBI's Framingham Heart Study: The SABRe CVD Initiative

The NHLBI's Framingham Heart Study (FHS), one of the world's preeminent observational study settings, is devoted to increasing scientific knowledge by establishing a public resource of data and samples. For nearly 60 years, the people of Framingham have generously volunteered their time to this high-profile study and remain deeply committed to its success. The Systems Approach to Biomarker Research in Cardiovascular Disease Initiative (SABRe CVD Initiative) will generate extensive biomarker data from 7000 FHS participants using multiple high throughput platforms including immunoassays, proteomics, metabolomics/lipomics, and gene expression and microRNA profiling. SABRe will generate thousands of new biomarkers from each participant, with data deposited with the NCBI and linked to the extensive phenotype and genotype data already in an NCBI data repository (as part of the NHLBI SHARe Genome-wide Association Project). All data from the SABRe, SHARe, and the nearly 60 years of phenotypic data from the FHS will be integrated into a massive resource that will be accessible to the outside scientific community in a manner consistent with the informed consent preferences of the Framingham participants.

SABRe CVD Projects

• Project 1: Discovery proteomics and metabolomics/lipomics in case-control studies of subclinical atherosclerosis, metabolic syndrome (300 cases, 300 controls), and predicting new cardiovascular events using samples obtained prior to event (150 cases, 300 controls).
• Project 2: Immunoassays of 180 circulating protein biomarkers of atherosclerosis and metabolic syndrome in 7400 FHS participants.
• Project 3: Gene expression profiling of WBC derived RNA to characterize the genomic signatures of atherosclerosis and metabolic syndrome in 5000-7000 FHS participants (lab work to take place at NHLBI Core Microarray Lab).
• Project 4: MicroRNA profiling of WBC derived RNA to characterize microRNA regulation of gene expression and the relations of microRNA to clinical traits and diseases. microRNA profiling will be conducted in 5000-7000 FHS participants.

The SABRe Initiative is a state-of-the-art research enterprise to advance personalized medicine through biomarker discovery and validation. This project holds great promise for identifying mechanisms of disease and promoting the development of new diagnostics and therapeutics for diseases of high impact.

The specific aims for SABRe CVD are as follows:
1. To identify the biomarker signatures of atherosclerosis as determined by: a) aortic and coronary calcification on CT (data available in 3500 people), b) aortic plaque burden by MRI (n=2000), c) carotid intimal-medial thickness by ultrasound (n=3500), d) clinical atherosclerotic CVD (n=500), and e) the dynamic balance between arterial calcification and bone demineralization (n=3500).

2. To identify the biomarker signatures of metabolic risk factors related to cardiovascular risk: a) systolic and diastolic blood pressure (n=7000), b) body mass index (n=7000) and visceral adiposity by CT (n=3500), c) dyslipidemia (lipid levels, n=7000), and d) impaired fasting glucose, diabetes, and insulin resistance (glucose and insulin levels, n=7000).

3. To identify genomic convergence (convergence of signals from genetic variation and gene expression) with SABRe biomarker levels and clinical traits and diseases.

Available Data sets

Currently we have the following data SABRe CVD data sets available in the 'Authorized Access' area of dbGaP.

Project 1:
We have 2 Px data sets posted:

1. iTRAQ Px data set of 135 case/control pairs
2. Targeted MRM Px of 33 targets measured in the CVD study of 658 samples.

1. LCMS Lipids from Metabolic Syndrome study
2. GCMS Mx from Metabolic Syndrome study

Project 2:
Immunoassay Panels 1-3 datasets and documents are included for ~7400 Framingham samples from Offspring Exam 7 and Gen III Exam 1 "SABRe_Project_2_Immunoassays_l_mpimn01_2005_m_0692s"

1. "SABRe_Project_2_Immunoassays_l_mpimn01_2005_m_0692s"
   • Panel I: Clusterin; Apo B-100; Apolipoprotein A1; LP(a); hsCRP
2. "SABRe_Project_2_Immunoassays_l_mpimn02_2005_m_0693s"
   • Panel II: Cystatin C; GDF-15; GMP-140; IGFBP-3; MMP-9; MPO; sGP130; slCAM; and TIMP-1
3. "SABRe_Project_2_Immunoassays_l_mpimn03_2005_m_0694s"
   • Panel III: IL-6; Osteocalcin; sCD40L; FGF-23; Troponin I; VEGF, Leptin-R; NT-Pro-BNP; MCP-1; sRAGE; Leptin; CXCL16 and Resistin
4. "SABRe_Project_2_Immunoassays_l_mpimn04_2005_m_0757s"
   • Panel IV: Angiopoietin-related protein 3(ANGPTL3), Contactin-1(CNTN1), Endostatin(COL18A1), Insulin-like growth factor -1(IGF-1), Myoglobin(MB), Plasminogen activator inhibitor 1(PAI-1), and Lithostathine-1-alpha(REG1A)
5. "SABRe_Project_2_Immunoassays_l_mpimn05_2005_m_0758s"
   • Panel V: (Stromal cell-derived factor 1 (SDF-1), Platelet glycoprotein V (GP5), Mid-region of proadrenomedullin (MR-Pro-ADM), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Project 3:
Expression dataset (phe000002.v2) is updated with Generation III (GENIII) exam 2 expression data and is repacked in accordance with new consent information. Please note that subject IDs were revised for 7 previously released FHS_OFFs samples. This data set includes Offspring exam 8 case-control, Offspring exam 8 cohort and GEN III expression data and reflects the completion of the gene expression data generation.

Project 4:
miRNA dataset SABRe_Project_4_miRNA_I_mrna_2011_m_0797s includes Offspring exam 8, case-control and Offspring exam 8 and Gen III miRNA data as a combined data set with variables to indicate case/control status as well as cohort status to differentiate the combined data set.

• Study Weblinks:
  • The Framingham Heart Study
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Cohort
• Total number of consented subjects: 7567
• Subject Sample Telemetry Report (SSTR)

Research milestones of the Framingham Heart Study can be found at http://www.framinghamheartstudy.org/about/milestones.html.

The Generation 1 (or Original) cohort Exam 1 took place between 1948 and 1953. Biennial exams have continued to the present. Exam 29 took place between 2006 and 2007. Exam 30 began in 2008.

The Generation 2 (or Offspring) cohort Exam 1 took place between 1971 and 1975. This cohort on average has been examined every three to four years. However, there was an eight year gap between Exam 1 and Exam 2 and a seven year gap between Exam 7 and Exam 8. Exam 8 took place between 2005 and 2008.

The Generation 3 cohort Exam 1 took place between 2002 and 2005. Exam 2 began in 2008.

The New Offspring Spouse cohort Exam 1 took place between 2003 and 2005. Exam 2 began in 2008.

• Primary Phenotype: Cardiovascular Diseases
• Cardiovascular System
• Myocardial Infarction
• Coronary Artery Bypass Grafting
• Percutaneous Transluminal Coronary Angioplasty
• Stroke

• Principal Investigator
  • Daniel Levy, MD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
• Co-Principal Investigators
  • Christopher O'Donnell, MD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Jane Freedman, MD. University of Massachusetts, Worcester, MA, USA.
• Principal Investigator-Bioinformatics
  • Peter J. Munson, PhD. Center for Information Technology, National Institutes of Health, Bethesda, MD, USA.
• Principal Investigator-Lab Operation
  • Nalini Raghavachari, PhD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
• Principal Investigator-Statistics
  • Martin G. Larson, SD. Department of Mathematics, Boston University, Boston, MA, USA.
• Investigators
  • Roby Joehanes, PhD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sai-xia Ying, PhD. Center for Information Technology, National Institutes of Health, Bethesda, MD, USA.
  • Andrew Johnson, PhD. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
• Funding Sources
  • Division of Intramural Research. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.