Post‐GWAS in Psychiatric Genetics: A Developmental Perspective on the “Other” Next Steps

Abstract

As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post-genome-wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.

Polygenic risk for alcohol misuse is moderated by romantic partnerships

“…To characterize individual risk across hundreds or thousands of alleles associated with an outcome in a GWAS, genome‐wide polygenic risk scores (GPS) have emerged as a way to aggregate this information into a single score. As we begin to identify GPS robustly associated with substance use and dependence, one of the critical next steps toward precision medicine will be to characterize the pathways by which risk unfolds . For alcohol‐related outcomes, this will necessitate characterizing how specific environments moderate the likelihood that individuals carrying risky genetic predispositions will develop excessive use, problems and dependence, providing important information about targeted areas for intervention.…”

Genetic moderation of the effects of the Family Check-Up intervention on children's internalizing symptoms: A longitudinal study with a racially/ethnically diverse sample

“…We examined internalizing psychopathology only at age 10 years, the only age when the Diagnostic Interview Schedule for Children—IV interview was conducted with children. Genetic and environmental influences can vary in their relevance to development at different ages, and thus our findings might be specific to middle childhood (Dick et al, 2017). Although our sample had adequate representation of European Americans, African Americans, and Latinos, we had little representation of other groups such as Native Americans and Asian Americans.…”

Polygenic Risk for Alcohol Misuse is Moderated by Romantic Partnerships: Primarily in Men

“…As we begin to identify GPS robustly associated with substance use and dependence, one of the critical next steps toward precision medicine will be to characterize the pathways by which risk unfolds. 22 For alcohol-related outcomes, this will necessitate characterizing how specific environments moderate the likelihood that individuals carrying risky genetic predispositions will develop excessive use, problems, and dependence, providing important information about targeted areas for intervention.…”