Effect-Size Estimation Using Semiparametric Hierarchical Mixture Models in Disease-Association Studies with Neuroimaging Data.

In disease-association studies using neuroimaging data, evaluating the biological or clinical significance of individual associations requires not only detection of disease-associated areas of the brain but also estimation of the magnitudes of the associations or effect sizes for individual brain areas. In this paper, we propose a model-based framework for voxel-based inferences under spatial dependency in neuroimaging data. Specifically, we employ hierarchical mixture models with a hidden Markov random field structure to incorporate the spatial dependency between voxels. A nonparametric specification is proposed for the effect size distribution to flexibly estimate the underlying effect size distribution. Simulation experiments demonstrate that compared with a naive estimation method, the proposed methods can substantially reduce the selection bias in the effect size estimates of the selected voxels with the greatest observed associations. An application to neuroimaging data from an Alzheimer's disease study is provided.