Simulation of a medication and methylation effects on triglycerides in the Genetic Analysis Workshop 20

Abstract

The GAW20 simulation data set is based upon the companion Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study fenofibrate clinical trial data set that forms the real data example for GAW20. The simulated data problem consists of 200 simulated replications of what might happen if we were to repeat the GOLDN clinical trial 200 independent times, for these exact same subjects, but using a new fictitious drug (called "genomethate") that has a pharmaco-epigenetic effect on triglyceride response. For each replication, the pre-genomethate values at visits 1 and 2 are constant (ie, pedigree structures, age, sex, all phenotypes, covariates, genome-wide association study (GWAS) genotypes, and visit 2 methylation values), the same as the real GOLDN data across all 200 replications. Only the post-genomethate treatment data (ie, methylation and triglyceride levels for visits 3 and 4) change across the 200 replications. We postulate a growth curve pharmaco-epigenetic response model, in which each patient's response to genomethate treatment is individualized, and is dependent upon their genotype as well as the methylation state for key genes.

Fig. 1

A 3D indexing order of the GAW20 simulation. The j index in the figure represents the subjects, the i index is noting the causal SNPs, where i = 1–5 also indexes the 5 main effects of the corresponding nearby CpG sites, while the sites 6–105 are 100 SNPs with background genetic effects. The k index indicates replications (k = 1, 2, …, R = 200)