Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: A population-based cohort study.


Background: Schizophrenia typically onsets after puberty but is often preceded by observable childhood neurodevelopmental impairments. Whether these childhood antecedents index genetic liability is unknown. We used polygenic risk scores derived from a patient discovery sample as indicators of the genetic liability of schizophrenia. Our aim was to identify the early childhood manifestations of this liability in a UK population-based cohort. Methods: The study sample was the Avon Longitudinal Study of Parents and Children, a prospective population-based cohort study of 14701 children. Data were primarily analysed with regression-based analyses. Polygenic risk score were generated from a published Psychiatric Genomics Consortium genome-wide association study. Outcomes were childhood (age 4-9 years) dimensional measures in four developmental domains with 12 indicators: cognition and learning, social and communication, emotion and mood regulation, and behaviour (n = 5100-6952). Findings: At age 7-9 years, schizophrenia polygenic risk scores showed associations with lower performance intelligence quotient (beta -0.056, OR 1.13 [95% CI 1.04-1.23]), poorer social understanding (beta -0.032, OR 1.08 [1.00-1.17]), worse language intelligibility and fluency (beta -0.032, OR 1.10 [1.02-1.20]), more irritability (beta 0.032, OR 1.07 [1.01-1.14]), and more headstrong behaviour (beta 0.031, OR 1.08 [1.02-1.15]). The schizophrenia polygenic risk scores also predicted social and behavioural impairments as early as age 4 years. Interpretation: Childhood cognitive, social, behavioural, and emotional impairments, implicated as antecedents to schizophrenia in high-risk, developmental studies, might represent early manifestations of genetic liability. Funding: Medical Research Council.