Dataset Information

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.

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.

SUBMITTER: Kraja AT

PROVIDER: S-EPMC2795938 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Kraja Aldi T AT Culverhouse Robert R Daw E Warwick EW Wu Jun J Van Brunt Andrew A Province Michael A MA Borecki Ingrid B IB

BMC proceedings 20091215

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 ...[more]

PMID: 20018031

Similar Datasets

Project description:BackgroundThere are many research studies have estimated the heritability of phenotypic traits, but few have considered longitudinal changes in several phenotypic traits together.ObjectiveTo evaluate the progressive effect of single nucleotide polymorphisms (SNPs) on prominent health-related phenotypic traits by determining SNP-based heritability ([Formula: see text]) using longitudinal data.MethodsSixteen phenotypic traits associated with major health indices were observed biennially for 6843 individuals with 10-year follow-up in a Korean community-based cohort. Average SNP heritability and longitudinal changes in the total period were estimated using a two-stage model. Average and periodic differences for each subject were considered responses to estimate SNP heritability. Furthermore, a genome-wide association study (GWAS) was performed for significant SNPs.ResultsEach SNP heritability for the phenotypic mean of all sixteen traits through 6 periods (baseline and five follow-ups) were significant. Gradually, the forced vital capacity in one second (FEV1) reflected the only significant SNP heritability among longitudinal changes at a false discovery rate (FDR)-adjusted 0.05 significance level ([Formula: see text], FDR = 0.0012). On estimating chromosomal heritability, chromosome 2 displayed the highest heritability upon periodic changes in FEV1. SNPs including rs2272402 and rs7209788 displayed a genome-wide significant association with longitudinal changes in FEV1 (P = 1.22 × 10-8 for rs2272402 and P = 3.36 × 10-7 for rs7209788). De novo variants including rs4922117 (near LPL, P = 2.13 × 10-15) of log-transformed high-density lipoprotein (HDL) ratios and rs2335418 (near HMGCR, P = 3.2 [Formula: see text] 10-9) of low-density lipoprotein were detected on GWAS.ConclusionSignificant genetic effects on longitudinal changes in FEV1 among the middle-aged general population and chromosome 2 account for most of the genetic variance.

Project description:Background:Simulation-based education (SBE) is increasingly endorsed as an educational strategy. It allows health-care professionals to practice clinical skills within a safe learning environment, and requires devices for simulation or simulated patients, trained teachers, and an appropriate environment. The objective of this study was to evaluate perceptions of participants on SBE and an SBE workshop. Methods:A 1-day SBE workshop was conducted on September 4, 2018, in collaboration with Laerdal Global Health Nepal and the National Centre for Health Professions Education (NCHPE), Institute of Medicine, Kathmandu, Nepal. Semistructured pretest and posttest questionnaires were used to evaluate the perceptions of participants regarding SBE and the effectiveness of the workshop. Data were analyzed using SPSS 21. Results:The mean difference in participant perceptions of SBE before and after participation in the workshop was significant (P<0.05) on seven statements: enhances communication skills (pretest 4.53±0.72, posttest 4.84±0.75; P=0.03), helps in seeing and managing even rarest of cases (pretest 3.59±1.00, posttest 4.21±0.92; P=0.02), overcomes the problem of uncooperative patients (pretest 3.12±0.93, posttest 3.95±1.22; P=0.004), increases confidence of students in dealing with real patients (pretest 4.29±0.77, posttest 4.79±0.42; P=0.041), enables preparation of rating scales for skills and attitude evaluation (pretest 3.76±0.83, posttest 4.11±0.76; P=0.049), provides immediate feedback during simulation (pretest 4.06±0.9, posttest 4.58±0.51; P=0.016), and keeps materials/equipment ready before simulation (pretest 4.29±0.68, posttest 4.79±0.53; P=0.007). Mean scores for participant feedback on the workshop using a Likert scale of 1-5 (5= strongly agree, 1= strongly disagree) were notable: objective of workshop fulfilled (4.16±0.688), session very interesting (4.37±0.597), session useful for future job (4.47±0.513), scenario relevant to subject (4.21±0.787), what I learnt will be useful in practice (4.05±0.78), resource persons/facilitators were helpful and effective (4.37±0.597), professional (4.42±0.507), and answered all questions (4.32±0.478), and course content was presented clearly (4.26±0.452). Almost all participants found the workshop useful and well presented, and suggested conducting such workshops frequently. Conclusion:The SBE workshop produced substantial differences in perceptions of participants. Participants found the workshop effective in improving knowledge and understanding of SBE.

Dataset Information

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.

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets