Abstract
The Genetic Analysis Workshop 13 simulated data aimed to mimic the major features of the real Framingham Heart Study data that formed Problem 1, but under a known inheritance model and with 100 replicates, so as to allow evaluation of the statistical properties of various methods. The pedigrees used were the 330 real pedigree structures (comprising 4692 individuals) with some minor changes to protect confidentiality. Fifty trait genes and 399 microsatellite markers were simulated by gene dropping on 22 autosomal chromosomes. Assuming random ascertainment of families, a system of eight longitudinal quantitative traits (designed to be similar to those in the real data) was generated with a wide range of heritabilities, including some pleiotropic and interactive effects. Genes could affect either the baseline level or the rate of change of the phenotype. Hypertension diagnosis and treatment were simulated with treatment availability, compliance, and efficacy depending on calendar year. Nongenetic traits of smoking and alcohol were generated as covariates for other traits. Death was simulated as a hazard rate depending upon age, sex, smoking, cholesterol, and systolic blood pressure.After the complete data were simulated, missing data indicators were generated based on logistic models fitted to the real data, involving the subject's history of previous missing values, together with that of their spouses, parents, siblings, and offspring, as well as marital status, only-child indicators, current value at certain simulated traits, and the data collection pattern on the cohort into which each subject was ascertained.
Highlights
Our goal in simulating data for Genetic Analysis Workshop 13 (GAW13) was to provide a data set with the basic features of the real data [1], a set of families from the Framingham Heart Study (FHS) [2], but under a known "true" inheritance model
The Framingham study has a number of unique features, but those we focused on replicating in our simulated set were the longitudinal collection over many years of several related traits on a large set of pedigrees and the availability of a complete genome screen with microsatellite markers
Intercept; Mij, indicator for subject i's visit j being missing; Mij, average missingness proportion for subject i up to and including visit j; MS, marital status; NA, indicator for parents' being not available in the data set; OC, only child; CHOL, cholesterol; WT, weight
Summary
Our goal in simulating data for Genetic Analysis Workshop 13 (GAW13) was to provide a data set with the basic features of the real data [1], a set of families from the Framingham Heart Study (FHS) [2], but under a known "true" inheritance model. We only allowed the genetic effects to interact with each other and the environmental effects additively or multiplicatively: we felt it was more important to focus our time on the longitudinal aspects of the model This simulated data set is designed to aid in the testing of methods, not to illustrate the workings of the human body. When indirect effects are considered as well, the picture is even more complex: all 50 trait loci have an effect, direct or indirect, on hypertension diagnosis and DBP We expect that this data set contains far more complexity than can be detected, even if all 100 simulated replicates of the data are analyzed simultaneously. We believe that this simulated set does mirror reality
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