Polygenic architecture of childhood emotional and behavioral problems in East Asian youth: a multivariate genome-wide study

Abstract Background Emotional and behavioral problems in childhood, commonly classified as internalizing and externalizing symptoms, represent early manifestations of vulnerability to later psychiatric disorders. However, their genetic architecture remains largely characterized in European populations, with limited evidence from East Asian cohorts. Methods We conducted the first multivariate genome-wide association study of 1,522 school-aged children from Taiwan. Using parent-reported Child Behavior Checklist (CBCL) scores and approximately 6 million SNPs, we jointly assess genetic associations across internalizing, externalizing, and total problem dimensions. Gene-based and tissue enrichment analyses were performed to examine biological relevance. To index shared polygenic liability across psychiatric disorders, we constructed a meta-polygenic risk score (metaPRS) via elastic-net regression integrating risk profiles from a number of major psychiatric conditions and examined its association with symptom dimensions and suicidal behaviors. Results A few genome-wide significant loci were identified (p < 5×10⁻⁸), including variants mapping to genes previously implicated in mood and neurodevelopmental pathways (e.g., BCL9 , ADARB2 , FGGY ). Tissue enrichment analyses highlighted expression patterns in brain regions central to emotion regulation, including the anterior cingulate cortex, hypothalamus, and cerebellum, as well as peripheral cardiac and intestinal tissues. The metaPRS accounted for modest but significant variance (0.92–1.26%) in internalizing and externalizing symptoms, and significantly predicted increased depressive symptoms and suicidal risk, highlighting the early emergence of transdiagnostic polygenic vulnerability. Conclusion These findings provide the first genomic characterization of childhood emotional and behavioral problems in East Asian youth. The results support a transdiagnostic polygenic liability underlying early psychopathology and underscore the importance of ancestry-diverse and multivariate approaches in advancing developmental risk stratification and precision mental health research.