Independent versus joint effects of polygenic or family-based schizophrenia risk in diverse ancestry youth in the ABCD study

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Detalles Bibliográficos
Publicado en:	Psychological Medicine vol. 55 (Oct 2025)
Autor principal:	Hyat, Mahnoor
Otros Autores:	Zhu, Jinhan, Boltz, Toni A., Conomos, Matthew P., Hughes, Dylan E., Fohner, Alison E., Foster, Katherine T., Bigdeli, Tim B., Forsyth, Jennifer K.
Publicado:	Cambridge University Press
Materias:	United States > US Genealogy Accuracy Cognition Psychopathology Schizophrenia Mental disorders Risk assessment Families & family life Affective disorders Standard scores Environmental aspects Externalizing problems Child Behavior Checklist Aggressive behavior Child development Psychosis Mental depression Associations Cognitive development Internalization Psychotic symptoms Cognitive-behavioral factors Intellectual development Emotional behavior Generalizability Children & youth Behavior Emotional disorders Childhood Youth Brain Behavior problems Children Liability Genetics Adolescent development Disorders Symptoms
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Descripción
Resumen:	Background Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability. Methods Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals. Results SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences. Conclusions SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.
ISSN:	0033-2917 1469-8978
DOI:	10.1017/S0033291725102304
Fuente:	Sociology Database