RNA Sequencing in the Framingham Heart Study Third Generation Cohort Exam 2

NCT03225183 | Completed

• 2 other identifiers: 99991713317-H-N133
• Study Type: observational
• Target: 1,700
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The Framingham Heart Study (FHS) was initiated by the U.S Public Health Service in 1948 and turned over to the newly established National Heart Institute in 1951. The FHS is now jointly led by the National Heart, Lung, and Blood Institute and Boston University. The FHS currently studies risk factors, and the genetics of heart and blood vessel disease, and other health conditions in three generations of study participants. Scientists want to use the data collected from this study to do more research. They want to use a technique that determines the sequence of ribonucleic acid (RNA) molecules. Objective: To study genes related to certain diseases and health conditions. These include heart and blood vessel diseases, lung and blood diseases, stroke, memory loss, and cancer. Eligibility: People in the FHS Third Generation cohort who already attended exam 2. Design: Researchers will study samples that have already been collected in the FHS. There will be no active examination or burden to participants. During FHS visits, participants gave blood samples. They gave permission for the blood to be used for genetic research. RNA will be generated from the samples. They will be given a new ID separate from any personal data. They will be stored in a secure FHS lab. The samples will be analyzed. Only certified researchers can access them. No study participants will be contacted in relation to this project. ...

Conditions

Cardiovascular Disease; Hypertension

Keywords

TOPMed; Blood Pressure; Long Noncoding RNA; Gene Expression; MicroRNA; Natural History

Outcome Measures

Primary Outcomes (3)

• 1. To relate transcriptomic variation to CVD and its risk factors (blood pressure, lipids, glycemia, adiposity, smoking, and alcohol), including evaluating RNAs as biomarkers of risk and establishing causation via Mendelian randomization

  Will look at CVD events related to RNA sequence. a. Characterize the relation of protein-coding gene expression to CVD and its risk factors; b. Characterize the relations of lncRNAs to CVD and risk factors; c. Characterize the relations of RNA splicing variation to CVD and its risk factors; d. Characterize the relations of allele-specific expression, and parent-oforigin allele specific expression, to CVD and its risk factors

  Observational

• 2. To determine the association of genetic sequence variation from whole genome sequencing with gene expression via RNA-seq.

  Will look at CVD events related to RNA sequence and add gene expression results to analysisa. Identify genetic variants associated with expression of protein coding RNAs (eQTLs); b. Identify genetic variants associated with alternative splicing (sQTLS); c. Identify genetic variants associated with expression of lncRNAs

  Observational

• 3. To relate complex transcriptomic variation to other blood-based omics

  Will look at CVD events related to RNA sequence and add Metabolic profiling data to analysis modela. Determine the association of transcriptomic variation with DNA methylation (methylome); b. Determine the association of transcriptomic variation with circulating protein levels (proteome); c. Determine the association of transcriptomic variation with circulating metabolites (metabolome)

  Observational

Study Arms (1)

1

Framingham Heart Study participants

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Framingham Heart Study participants

You may qualify if:

• To accomplish the Aims of this project we propose to conduct RNA-seq on FHS Third Generation cohort participants with WGS as part of TOPMed. This can only be accomplished in FHS Third Generation cohort participants who attended exam 2 when PaxGene tubes were collected for RNA isolation. Therefore, we propose to conduct RNA-seq on FHS Third Generation cohort exam 2 attendees with PaxGene tubes (total n=3300) and in whom we will have direct or imputed WGS from TOPMed (n=1700).

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

Framingham Heart Study

Framingham, Massachusetts, 01702, United States

Location

Related Publications (3)

• Yao C, Chen BH, Joehanes R, Otlu B, Zhang X, Liu C, Huan T, Tastan O, Cupples LA, Meigs JB, Fox CS, Freedman JE, Courchesne P, O'Donnell CJ, Munson PJ, Keles S, Levy D. Integromic analysis of genetic variation and gene expression identifies networks for cardiovascular disease phenotypes. Circulation. 2015 Feb 10;131(6):536-49. doi: 10.1161/CIRCULATIONAHA.114.010696. Epub 2014 Dec 22.

  PMID: 25533967 BACKGROUND

• Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, Chen BH, Liu C, Joehanes R, Johnson AD, Yao C, Ying SX, Courchesne P, Milani L, Raghavachari N, Wang R, Liu P, Reinmaa E, Dehghan A, Hofman A, Uitterlinden AG, Hernandez DG, Bandinelli S, Singleton A, Melzer D, Metspalu A, Carstensen M, Grallert H, Herder C, Meitinger T, Peters A, Roden M, Waldenberger M, Dorr M, Felix SB, Zeller T; International Consortium for Blood Pressure GWAS (ICBP); Vasan R, O'Donnell CJ, Munson PJ, Yang X, Prokisch H, Volker U, van Meurs JB, Ferrucci L, Levy D. A meta-analysis of gene expression signatures of blood pressure and hypertension. PLoS Genet. 2015 Mar 18;11(3):e1005035. doi: 10.1371/journal.pgen.1005035. eCollection 2015 Mar.

  PMID: 25785607 BACKGROUND

• Joehanes R, Johnson AD, Barb JJ, Raghavachari N, Liu P, Woodhouse KA, O'Donnell CJ, Munson PJ, Levy D. Gene expression analysis of whole blood, peripheral blood mononuclear cells, and lymphoblastoid cell lines from the Framingham Heart Study. Physiol Genomics. 2012 Jan 18;44(1):59-75. doi: 10.1152/physiolgenomics.00130.2011. Epub 2011 Nov 1.

  PMID: 22045913 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases

Study Officials

• Daniel Levy, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 21, 2017
• Study Start: July 14, 2017
• Primary Completion: March 15, 2019
• Study Completion: June 17, 2019
• Last Updated: June 15, 2022

Record last verified: 2022-06

Locations

US (1)