Integration with systems biology approaches and -omics data to characterize risk variation

Researchers have identified hundreds of genetic variants that confer risk for psychiatric disorders. In order to inform disorder etiology and treatment, we are now faced with the task of uncovering the regulatory regions, genes, developmental stages, and functional pathways underlying this genetic risk. Notable challenges in the interpretation of risk variation include polygenicity, pleiotropy, patterns of linkage disequilibrium, and frequent location in noncoding regions of the genome. Here, we outline current approaches to annotate psychiatric disorder risk variation, including functional genomic annotation, transcriptome-wide association studies, studies of context-dependent gene regulation, and the aggregation of risk variants to gene networks and pathways. We focus particularly on noncoding variants derived from genome-wide association studies, due to both the unique considerations and methodological advancements in this field.