Abstract

? ? The Family Blood Pressure Program [FBPP] is an unprecedented collaboration to identify genes influencing blood pressure levels, hypertension and its cardiovascular complications (hereafter referred to as """"""""hypertension genes""""""""). To date, the Program has carried out 21,600 physical examinations, assembled a shared database of 294 hypertension-relevant variables, measured quantitative echocardiograms on 7,321 individuals, carried-out genome-wide linkage analyses for hypertension status and 13 related phenotypes, published (or in press) 128 manuscripts and identified 5 hypertension susceptibility genes by following-up 4 linkage peaks. In the proposed next phase of the FBPP, a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world.
In Aim 1, we will build, maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension, its risk factors and its complications.
In Aim 2, we will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes.
In Aim 3, we will use a combination of bioinformatics, a dense array of SNPs, and state-of-the-art ? data analysis to follow-up regions of interest and identify the underlying hypertension genes. The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase.
In Aim 4, we will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension, including left ventricular mass and microalbuminuria. It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension, including its risk factors, complications, and response to treatment. ? (End of Abstract) ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL054471-13
Application #
7283155
Study Section
Special Emphasis Panel (ZHL1-CSR-L (M1))
Program Officer
Paltoo, Dina
Project Start
1995-09-05
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2010-08-31
Support Year
13
Fiscal Year
2007
Total Cost
$703,442
Indirect Cost

  Institution

Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

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
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
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:

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