Delineating Additional Risk Factors

Excerpt

This chapter highlights paths, processes, and considerations that become important as we build on the initial success of large genome-wide association studies of psychiatric disorders. As such, it largely focuses on research on common genetic variation and human genetic research. It proposes directing research toward interrogating how genetic variation acts on the developing brain. For this reason, it discusses the potential value and pitfalls of using developmental, circuit-based, and quantitative symptom-based phenotypes in parallel to the traditional approach of reliance on binary diagnoses in genetic research designs. With respect to heterogeneity and co-occurrence present in psychiatric disorders, analytic approaches are outlined that can advance understanding, improve gene discovery, and potentially influence nosology. It argues that increasing cohort diversity is nonnegotiable: it is essential to improve gene discovery, translation, social justice, and research equity. Furthermore, a range of methods that interrogate the processes of environmental risk, gene–environment correlation, and gene–environment interaction enable a more accurate understanding of direct genetic effects and of how environments operate together with genetic risk for psychiatric disorders. Far from being a diversion, these environmentally informed methods are likely to catalyze biological insights. To this end, considerations for optimal future experimental study designs are discussed, outlining their characteristics and the prioritized approaches. The overarching goal is to deliver, through gene discovery research, translational benefits for individuals living with neurodevelopmental conditions and psychiatric disorders.