Application of Genetic Algorithms to the Discovery of Complex Models for Simulation Studies in Human Genetics.

Simulation studies are useful in various disciplines for a number of reasons including the development and evaluation of new computational and statistical methods. This is particularly true in human genetics and genetic epidemiology where new analytical methods are needed for the detection and characterization of disease susceptibility genes whose effects are complex, nonlinear, and partially or solely dependent on the effects of other genes. Despite this need, the development of complex genetic models that can be used to simulate data is not always intuitive. In fact, only a few such models have been published. In this paper, we present a strategy for identifying complex genetic models for simulation studies that utilizes genetic algorithms. The genetic models used in this study are penetrance functions that define the probability of disease given a specific DNA sequence variation has been inherited. We demonstrate that the genetic algorithm approach routinely identifies interesting and useful penetrance functions in a human-competitve manner.