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Kraja AT, Culverhouse R, Daw EW, et al. The Genetic Analysis Workshop 16 Problem 3: simulation of heritable longitudinal cardiovascular phenotypes based on actual genome-wide single-nucleotide polymorphisms in the Framingham Heart Study. BMC Proc. 2009;3:S4doi: 10.1186/1753-6561-3-s7-s4.
Kraja, A. T., Culverhouse, R., Daw, E. W., Wu, J., Van Brunt, A., Province, M. A., & Borecki, I. B. (2009). The Genetic Analysis Workshop 16 Problem 3: simulation of heritable longitudinal cardiovascular phenotypes based on actual genome-wide single-nucleotide polymorphisms in the Framingham Heart Study. BMC proceedings, 3S4. https://doi.org/10.1186/1753-6561-3-s7-s4
Kraja, Aldi T, et al. "The Genetic Analysis Workshop 16 Problem 3: simulation of heritable longitudinal cardiovascular phenotypes based on actual genome-wide single-nucleotide polymorphisms in the Framingham Heart Study." BMC proceedings vol. 3 (2009): S4. doi: https://doi.org/10.1186/1753-6561-3-s7-s4
Kraja AT, Culverhouse R, Daw EW, Wu J, Van Brunt A, Province MA, Borecki IB. The Genetic Analysis Workshop 16 Problem 3: simulation of heritable longitudinal cardiovascular phenotypes based on actual genome-wide single-nucleotide polymorphisms in the Framingham Heart Study. BMC Proc. 2009 Dec 15;3:S4. doi: 10.1186/1753-6561-3-s7-s4. PMID: 20018031; PMCID: PMC2795938.
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BMC Proc. 2009 Dec 15;3:S4. doi: 10.1186/1753-6561-3-s7-s4.

The Genetic Analysis Workshop 16 Problem 3: simulation of heritable longitudinal cardiovascular phenotypes based on actual genome-wide single-nucleotide polymorphisms in the Framingham Heart Study.

BMC proceedings

Aldi T Kraja, Robert Culverhouse, E Warwick Daw, Jun Wu, Andrew Van Brunt, Michael A Province, Ingrid B Borecki

Affiliations

  1. Division of Statistical Genomics, Washington University School of Medicine, 4444 Forest Park Boulevard, Campus Box 8506, St, Louis, Missouri 63108, USA. [email protected].

PMID: 20018031 PMCID: PMC2795938 DOI: 10.1186/1753-6561-3-s7-s4

Abstract

The Genetic Analysis Workshop (GAW) 16 Problem 3 comprises simulated phenotypes emulating the lipid domain and its contribution to cardiovascular disease risk. For each replication there were 6,476 subjects in families from the Framingham Heart Study (FHS), with their actual genotypes for Affymetrix 550 k single-nucleotide polymorphisms (SNPs) and simulated phenotypes. Phenotypes are simulated at three visits, 10 years apart. There are up to 6 "major" genes influencing variation in high- and low-density lipoprotein cholesterol (HDL, LDL), and triglycerides (TG), and 1,000 "polygenes" simulated for each trait. Some polygenes have pleiotropic effects. The locus-specific heritabilities of the major genes range from 0.1 to 1.0%, under additive, dominant, or overdominant modes of inheritance. The locus-specific effects of the polygenes ranged from 0.002 to 0.15%, with effect sizes selected from negative exponential distributions. All polygenes act independently and have additive effects. Individuals in the LDL upper tail were designated medicated. Subjects medicated increased across visits at 2%, 5%, and 15%. Coronary artery calcification (CAC) was simulated using age, lipid levels, and CAC-specific polymorphisms. The risk of myocardial infarction before each visit was determined by CAC and its interactions with smoking and two genetic loci. Smoking was simulated to be commensurate with rates reported by the Centers for Disease Control. Two hundred replications were simulated.

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