Copy Number Variations and Human Well-Being: Integrating Psychiatric, Physical, and Socioeconomic Perspectives

Copy number variations (CNVs) have emerged as crucial genetic factors that influence a wide spectrum of human health outcomes, with particularly strong associations to psychiatric disorders. In this review, we present a synthesis of diverse impacts of psychiatric disorder-associated CNVs on neurodevelopment, brain function, and physical health across the lifespan. Large-scale studies have revealed that CNV carriers exhibit an increased risk for psychiatric disorders, cognitive deficits, sleep disturbances, neurological disorders, and other physical conditions, including cardiovascular diseases, diabetes, and renal disease, highlighting the wide-ranging impact of CNVs beyond the brain. Neuroimaging studies have revealed substantial CNV effects on brain structure, from cortical and subcortical alterations to white matter microstructure, with effect sizes often exceeding those observed in idiopathic psychiatric disorders. Cellular and animal models have begun to elucidate dynamic CNV effects on neurodevelopment, neuronal function, and cellular energy metabolism, while revealing complex CNV-environment interactions and cell type-specific responses, particularly in studies of 22q11.2 deletion syndrome. This review also explores the complex interplay between psychiatric and physical health conditions in CNV carriers and how these interactions contribute to adverse socioeconomic outcomes, including reduced educational attainment and income levels, creating a feedback loop that further impacts health outcomes. Finally, in this review, we also highlight research limitations and propose key priorities for clinical implementation, including the need for longitudinal studies, standardized guidelines for CNV result reporting and genetic counseling, and integrated care networks to provide a foundation for advancing the field of precision psychiatry.