The purpose of the proposed study, Genetics of Coronary and Aortic Calcification (GENCAC), is to identify genetic factors that establish susceptibility to (a) coronary and aortic atherosclerosis and (b) inter- individual variability in the inflammatory response. We propose to quantify coronary and aortic artery calcium volume in 441 selected, informative pedigrees (3,000 individuals) previously examined and extensively genotyped (400 markers spanning the genome) by the NHLBI Family Heart Study, in order to identify genes associated with human atherosclerosis. An additional 275 African American sibships (- 600 individuals, also examined and comparably genotyped) will be included to address these study questions in this high-risk population. Assessment of the inter-individual variability in the inflammatory burden and the host response, and the extensive metabolic, behavioral, and environmental data already collected on these pedigrees will provide enhanced phenotypic homogeneity and increased analytic power in assessing the genetic basis of atherosclerosis. State of the art laboratory and statistical methods will be used to find, localize and characterize the influence of predisposing genes to atherosclerosis and the inflammatory response. Novel genetic analysis methods will be used to address the issues of phenotypic, genetic and population heterogeneity, epistasis, complex interactions among the genetic and environmental risk factors, and to optimize the detection of genomic regions affecting phenotypic susceptibility. The notorious issue of multiple comparisons in genome scans will be bypassed with the use of novel global testing procedures. Based on a cost-efficient design of informative pedigrees and employing novel methodology, this study will contribute currently unavailable information on genetic and environmental determinants of atherosclerosis, with a focus on the prevention of this widely prevalent condition associated with high burden of costs to society. This application corresponds to the GENCAC Network Core submitted by the University of North Carolina at Chapel Hill as part of the GENCAC genetic epidemiology network.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01HL067893-01
Application #
6364645
Study Section
Special Emphasis Panel (ZHL1-CSR-L (M1))
Program Officer
Silsbee, Lorraine M
Project Start
2001-09-17
Project End
2005-08-31
Budget Start
2001-09-17
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$205,643
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
Mack, Salome; Coassin, Stefan; Rueedi, Rico et al. (2017) A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms. J Lipid Res 58:1834-1844
Patel, Yash R; Gadiraju, Taraka V; Ellison, R Curtis et al. (2017) Coffee consumption and calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study. Clin Nutr ESPEN 17:18-21
Nielson, Carrie M; Liu, Ching-Ti; Smith, Albert V et al. (2016) Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2. J Bone Miner Res 31:2085-2097
Imran, Tasnim F; Patel, Yash; Ellison, R Curtis et al. (2016) Walking and Calcified Atherosclerotic Plaque in the Coronary Arteries: The National Heart, Lung, and Blood Institute Family Heart Study. Arterioscler Thromb Vasc Biol 36:1272-7
Lai, Lana Y H; Petrone, Andrew B; Pankow, James S et al. (2015) Lack of association of apolipoprotein E (Apo E) polymorphism with the prevalence of metabolic syndrome: the National Heart, Lung and Blood Institute Family Heart Study. Diabetes Metab Res Rev 31:582-7
Hunt, Steven C; Kimura, Masayuki; Hopkins, Paul N et al. (2015) Leukocyte telomere length and coronary artery calcium. Am J Cardiol 116:214-8
Robbins, Jeremy M; Petrone, Andrew B; Carr, J Jeffrey et al. (2015) Association of ideal cardiovascular health and calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J 169:371-378.e1
Robbins, Jeremy M; Petrone, Andrew B; Ellison, R Curtis et al. (2014) Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study. ESPEN J 9:e131-e135
Miedema, Michael D; Petrone, Andrew B; Arnett, Donna K et al. (2014) Adult height and prevalence of coronary artery calcium: the National Heart, Lung, and Blood Institute Family Heart Study. Circ Cardiovasc Imaging 7:52-7
Lai, Y H Lana; Petrone, Andrew B; Pankow, James S et al. (2013) Association of dietary omega-3 fatty acids with prevalence of metabolic syndrome: the National Heart, Lung, and Blood Institute Family Heart Study. Clin Nutr 32:966-9

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