INTEGRATIVE BAYESIAN ANALYSIS OF NEUROIMAGING-GENETIC DATA THROUGH HIERARCHICAL DIMENSION REDUCTION.

Advances in neuromedicine have emerged from endeavors to elucidate the distinct genetic factors that influence the changes in brain structure that underlie various neurological conditions. We present a framework for examining the extent to which genetic factors impact imaging phenotypes described by voxel-wise measurements organized into collections of functionally relevant regions of interest (ROIs) that span the entire brain. Statistically, the integration of neuroimaging and genetic data is challenging. Because genetic variants are expected to impact different regions of the brain, an appropriate method of inference must simultaneously account for spatial dependence and model uncertainty. Our proposed framework combines feature extraction using generalized principal component analysis to account for inherent short- and long-range structural dependencies with Bayesian model averaging to effectuate variable selection in the presence of multiple genetic variants. The methods are demonstrated on a cocaine dependence study to identify ROIs associated with genetic factors that impact diffusion parameters.