Integrative Bayesian analysis of neuroimaging-genetic data with application to cocaine dependence

Neuroimaging and genetic studies provide distinct and complementary information about the structural and biological aspects of a disease. Integrating the two sources of data facilitates the investigation of the links between genetic variability and brain mechanisms among different individuals for various medical disorders. This article presents a general statistical framework for integrative Bayesian analysis of neuroimaging-genetic (iBANG) data, which is motivated by a neuroimaging-genetic study in cocaine dependence. Statistical inference necessitated the integration of spatially dependent voxel-level measurements with various patient-level genetic and demographic characteristics under an appropriate probability model to account for the multiple inherent sources of variation. Our framework uses Bayesian model averaging to integrate genetic information into the analysis of voxel-wise neuroimaging data, accounting for spatial correlations in the voxels. Using multiplicity controls based on the false discovery rate, we delineate voxels associated with genetic and demographic features that may impact diffusion as measured by fractional anisotropy (FA) obtained from DTI images. We demonstrate the benefits of accounting for model uncertainties in both model fit and prediction. Our results suggest that cocaine consumption is associated with FA reduction in most white matter regions of interest in the brain. Additionally, gene polymorphisms associated with GABAergic, serotonergic and dopaminergic neurotransmitters and receptors were associated with FA.