A framework to monitor environment-induced major genes for developmental trajectories: implication for a prenatal cocaine exposure study.

Whether there are specific genes involved in response to different environmental agents and how such genes regulate developmental trajectories during lifetime are of fundamental importance in health, clinical and pharmaceutical research. In this article, we present a novel statistical model for monitoring environment-induced genes of major effects on longitudinal outcomes of a trait. This model is derived within the maximum likelihood framework, incorporated by mathematical aspects of growth and developmental processes. A typical structural model is implemented to approximate time-dependent covariance matrices for the longitudinal trait. This model allows for a number of biologically meaningful hypothesis tests regarding the effects of major genes on overall growth trajectories or particular stages of development. It can be used to test whether and how major genetic effects are expressed differently under altered environmental agents. In a well-designed case-control study, our model has been employed to detect cocaine-dependent genes that affect growth trajectories for head circumference during childhood. The detected gene triggers significant effects on growth curves in both cocaine-exposed (case) and unexposed groups (control), but with different extents. Significant genotype-environment interactions due to this so-called environment-sensitive gene are promising for further studies toward its genomic mapping using polymorphic molecular markers.