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

Abstract

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 (β -0·056, OR 1·13 [95% CI 1·04-1·23]), poorer social understanding (β -0·032, OR 1·08 [1·00-1·17]), worse language intelligibility and fluency (β -0·032, OR 1·10 [1·02-1·20]), more irritability (β 0·032, OR 1·07 [1·01-1·14]), and more headstrong behaviour (β 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.