The NHLBI Family Blood Pressure Program is made up of four cooperating networks whose overall objective is to localize and characterize genes contributing to variation in blood pressure levels and hypertension status. The four networks were originally separately funded and competitive, but two critical realizations have led to full cooperation and collaboration. First, the oligogenic nature of blood pressure control dictates that large samples are necessary to achieve adequate statistical power for genomic linkage and association analyses. Second, linkage intervals are broad and contain large numbers of genes, so that success in identifying genes and mutations requires the effort of multiple laboratories freely sharing information. This coordination extends far beyond phenotyping and genotyping and is best exemplified by the Program's creation of a pooled data set and agreements about coordinated publications. During the initial funding period, the Program surpassed its original recruitment goals, carried out multiple genome-wide linkage and association analyses and created an interim pooled data set consisting of phenotype and genotype data from more than 10,000 individuals. In this renewal application, the Program proposes five specific aims to be carried out by all four networks.
These aims can be grouped according to two complementary themes: First, these applicants will create and analyze a database of blood pressure- related phenotype and genotype data from all FBPP participants (Aim 1). Within linked regions, they will identify allelic variation within positional candidate genes and evaluate the relationship of these polymorphisms with blood pressure levels and hypertension status (Aims 2 and 3). Second, they will use quantitative measures of target organ damage to identify genes that influence susceptibility to develop hypertensive heart and kidney diseases (Aims 4 and 5). In addition to the Program specific aims, each network proposes specific aims to be carried out by that network alone, based on unique aspects of their population and interests and expertise of the investigators. The Family Blood Pressure Program represents the most determined multidisciplinary approach to the genetics of hypertension ever assembled. The resulting synthesis of ideas and amassed data permits rigorous hypothesis testing not otherwise possible and will hasten understanding of the previously elusive genetic variation responsible for disease risk.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL054509-07
Application #
6389490
Study Section
Special Emphasis Panel (ZHL1-CSR-L (F1))
Program Officer
Old, Susan E
Project Start
1995-09-05
Project End
2005-06-30
Budget Start
2001-08-01
Budget End
2002-06-30
Support Year
7
Fiscal Year
2001
Total Cost
$231,048
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Irvin, Marguerite R; Sitlani, Colleen M; Noordam, Raymond et al. (2018) Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry. Pharmacogenomics J :
Wild, Philipp S; Felix, Janine F; Schillert, Arne et al. (2017) Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. J Clin Invest 127:1798-1812
Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon et al. (2017) Telomeres and the natural lifespan limit in humans. Aging (Albany NY) 9:1130-1142
Nandakumar, Priyanka; Lee, Dongwon; Richard, Melissa A et al. (2017) Rare coding variants associated with blood pressure variation in 15?914 individuals of African ancestry. J Hypertens 35:1381-1389
Selvaraj, Senthil; Djoussé, Luc; Aguilar, Frank G et al. (2017) Association of Estimated Sodium Intake With Adverse Cardiac Structure and Function: From the HyperGEN Study. J Am Coll Cardiol 70:715-724
Wang, Heming; Choi, Yoonha; Tayo, Bamidele et al. (2017) Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome. Genet Epidemiol 41:122-135
Taylor, Jacquelyn Y; Schwander, Karen; Kardia, Sharon L R et al. (2016) A Genome-wide study of blood pressure in African Americans accounting for gene-smoking interaction. Sci Rep 6:18812
Olfson, E; Saccone, N L; Johnson, E O et al. (2016) Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans. Mol Psychiatry 21:601-7
Selvaraj, Senthil; Martinez, Eva E; Aguilar, Frank G et al. (2016) Association of Central Adiposity With Adverse Cardiac Mechanics: Findings From the Hypertension Genetic Epidemiology Network Study. Circ Cardiovasc Imaging 9:
Aguilar, Frank G; Selvaraj, Senthil; Martinez, Eva E et al. (2016) Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study. Echocardiography 33:386-97

Showing the most recent 10 out of 39 publications