Mixed effects smoothing spline analysis of variance

We propose a general family of nonparametric mixed effects models. Smoothing splines are used to model the fixed effects and are estimated by maximizing the penalized likelihood function. The random effects are generic and are modelled parametrically by assuming that the covariance function depends on a parsimonious set of parameters. These parameters and the smoothing parameter are estimated simultaneously by the generalized maximum likelihood method. We derive a connection between a nonparametric mixed effects model and a linear mixed effects model. This connection suggests a way of fitting a nonparametric mixed effects model by using existing programs. The classical two-way mixed models and growth curve models are used as examples to demonstrate how to use smoothing spline analysis-of-variance decompositions to build nonparametric mixed effects models. Similarly to the classical analysis of variance, components of these nonparametric mixed effects models can be interpreted as main effects and interactions. The penalized likelihood estimates of the fixed effects in a two-way mixed model are extensions of James–Stein shrinkage estimates to correlated observations. In an example three nested nonparametric mixed effects models are fitted to a longitudinal data set.