Novel Functional Genomics Approaches Bridging Neuroscience and Psychiatry

The possibility of establishing a metric of individual genetic risk for a particular disease or trait has sparked the interest of the clinical and research communities, with many groups developing and validating genomic profiling methodologies for their potential application in clinical care. Current approaches for calculating genetic risk to specific psychiatric conditions consist of aggregating genome-wide association studies–derived estimates into polygenic risk scores, which broadly represent the number of inherited risk alleles for an individual. While the traditional approach for polygenic risk score calculation aggregates estimates of gene-disease associations, novel alternative approaches have started to consider functional molecular phenotypes that are closer to genetic variation and are less penalized by the multiple testing required in genome-wide association studies. Moving the focus from genotype-disease to genotype–gene regulation frameworks, these novel approaches incorporate prior knowledge regarding biological processes involved in disease and aggregate estimates for the association of genotypes and phenotypes using multi-omics data modalities. In this review, we discuss and list different functional genomics tools that can be used and integrated to inform researchers and clinicians for a better understanding and diagnosis of psychopathology. We suggest that these novel approaches can help generate biologically driven hypotheses for polygenic signals that can ultimately serve the clinical community as potential biomarkers of psychiatric disease susceptibility.