Potential for Genomics to Help Guide Preventive Strategies in Psychiatry.

Importance: Psychiatric disorders are a major source of disability and premature mortality worldwide. Advances in genomics have clarified parts of their genetic architecture, prompting questions about whether genomic information can inform preventive strategies for psychiatric disorders in clinical practice. This Special Communication describes potential benefits and harms of using genomic information, particularly polygenic scores (PGSs) and rare variants, to guide prevention in psychiatry. Observations: Broad application of genomic testing in universal or selective primary prevention is not currently supported by evidence of net clinical benefit, given modest absolute risk differences, limited individual-level predictive performance, and the potential for psychological harm. The possible value of genomic testing increases for indicated primary prevention, as prior probability rises and diagnostic uncertainty becomes clinically relevant. The most compelling opportunity lies in early care after individuals enter the psychiatric treatment system but before diagnostic trajectories fully crystallize. In this zone of diagnostic uncertainty, testing for rare, high-impact variants can shorten diagnostic delays, inform prognosis, and guide monitoring and treatment, provided that results are communicated appropriately. PGSs may contribute to risk stratification when applied in high-risk clinical populations and integrated with nongenetic factors. In secondary and tertiary prevention, pharmacogenomics provides actionable benefits for medication choice and safety, and rare variant testing has clear value in selected instances. Beyond psychiatric outcomes, genomic testing could potentially help address the profound mortality gap in severe mental illness by identifying elevated risk for somatic comorbidities, thus supporting more proactive, integrated care. Conclusions and Relevance: Currently, genomic testing in psychiatry should not be used for population-wide screening but may have value as a targeted clinical resource whose utility depends on timing, context, and purpose. When applied judiciously and embedded within comprehensive, ethically grounded care pathways, genomic testing holds promise as one component of a more precise, preventive, and patient-centered psychiatry.