Component 3, C. Sing, PI, is an integral part of this Collaborative Research Project grant entitled Modeling DNA Diversity in Reverse Cholesterol Transport involving two other components: population based genomics and DNA genotyping, (Component 1, E. Boerwinkle, PI) and population genetic analysis (Component 2, A. Clark, PI). Although there is a division of labor among components for practical and institutional purposes, the co-investigators and consultants engaged in this project will work as a team to develop resources to address one of the most complex and challenging problems in medicine, how is DNA sequence variation related to variation in human health in the population at large? Component 3 will develop models and test hypotheses about the relationship between DNA sequence variation (identified by Component I and genotyped in samples from the population at large) and variation in measures of health using reverse cholesterol transport (RCT) as the intermediate biological link between the genome and risk to cardiovascular health in the population at large. To accomplish this goal we will utilize information about population structure and genome organization established by Component 2 to: 1) develop new analytical tools (combinatorial partitioning, Bayesian methods, neural networks, etc.) for predicting interindividual variation in risk of cardiovascular disease using DNA sequence variation and 2) identify the variable DNA sites in 62 candidate genes that predict interindividual variation in measures of RCT in population-based samples that are representative of 2007 African-Americans and 2139 European-Americans at baseline and at each of four follow-up times.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072905-03
Application #
6888980
Study Section
Special Emphasis Panel (ZHL1-CSR-L (F1))
Program Officer
Sholinsky, Phyliss
Project Start
2003-06-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
3
Fiscal Year
2005
Total Cost
$648,591
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Genetics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Dyson, Greg et al. (2015) Subgroups at high risk for ischaemic heart disease:identification and validation in 67?000 individuals from the general population. Int J Epidemiol 44:117-28
Dyson, Greg; Sing, Charles F (2014) Efficient identification of context dependent subgroups of risk from genome-wide association studies. Stat Appl Genet Mol Biol 13:217-26
Lusk, Christine M; Dyson, Greg; Clark, Andrew G et al. (2014) Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study. Hum Genet 133:1105-16
Koester, Benjamin; Rea, Thomas J; Templeton, Alan R et al. (2012) Long-range autocorrelations of CpG islands in the human genome. PLoS One 7:e29889
Stengard, Jari H; Dyson, Greg; Frikke-Schmidt, Ruth et al. (2010) Context-dependent associations between variation in risk of ischemic heart disease and variation in the 5' promoter region of the apolipoprotein E gene in Danish women. Circ Cardiovasc Genet 3:22-30
Coventry, Alex; Bull-Otterson, Lara M; Liu, Xiaoming et al. (2010) Deep resequencing reveals excess rare recent variants consistent with explosive population growth. Nat Commun 1:131
Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne; Schnohr, Peter et al. (2010) Common clinical practice versus new PRIM score in predicting coronary heart disease risk. Atherosclerosis 213:532-8
Dyson, Greg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G et al. (2009) Modifications to the Patient Rule-Induction Method that utilize non-additive combinations of genetic and environmental effects to define partitions that predict ischemic heart disease. Genet Epidemiol 33:317-24
Klos, Kathy; Shimmin, Lawrence; Ballantyne, Christie et al. (2008) APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels. Hum Mol Genet 17:2039-46
Stengard, J H; Frikke-Schmidt, R; Tybjaerg-Hansen, A et al. (2007) Variation in 5'promoter region of the APOE gene contributes to predicting ischemic heart disease (IHD) in the population at large: the Copenhagen City Heart Study. Ann Hum Genet 71:762-71

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