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 #
5U01HL054473-07
Application #
6389481
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
$692,941
Indirect Cost
Name
Washington University
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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
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
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:
Mangino, Massimo; Christiansen, Lene; Stone, Rivka et al. (2015) DCAF4, a novel gene associated with leucocyte telomere length. J Med Genet 52:157-62
Katz, Daniel H; Selvaraj, Senthil; Aguilar, Frank G et al. (2014) Association of low-grade albuminuria with adverse cardiac mechanics: findings from the hypertension genetic epidemiology network (HyperGEN) study. Circulation 129:42-50
Selvaraj, Senthil; Aguilar, Frank G; Martinez, Eva E et al. (2014) Association of comorbidity burden with abnormal cardiac mechanics: findings from the HyperGEN study. J Am Heart Assoc 3:e000631
Simino, Jeannette; Shi, Gang; Weder, Alan et al. (2014) Body mass index modulates blood pressure heritability: the Family Blood Pressure Program. Am J Hypertens 27:610-9
Simino, Jeannette; Kume, Rezart; Kraja, Aldi T et al. (2014) Linkage analysis incorporating gene-age interactions identifies seven novel lipid loci: the Family Blood Pressure Program. Atherosclerosis 235:84-93
Glasser, Stephen P; Lynch, Amy I; Devereux, Richard B et al. (2014) Hemodynamic and echocardiographic profiles in African American compared with White offspring of hypertensive parents: the HyperGEN study. Am J Hypertens 27:21-6

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