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

Background. Schizophrenia typically onsets after puberty but is commonly preceded by observable childhood neurodevelopmental impairments. It is unknown if these childhood antecedents index genetic liability. We used polygenic risk scores (PRS) derived from a patient discovery sample as indicators of schizophrenia genetic liability. Our aim was to identify the early childhood manifestations of this liability in a UK population-based cohort. Method. Data were primarily analyzed using regression-based analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC). PRS 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 (12 indicators were explored): cognition/learning, social/communication, emotion/mood regulation and behavior (N=5100-6952). Outcomes. At age 7-9 years schizophrenia PRS showed associations with lower performance IQ (β=-0·056, OR=1.13), poorer social understanding (β=-0·032, OR=1·06), worse language intelligibility/fluency (β=-0·032, OR=1·10), irritability (β=0·032, OR=1·07) and headstrong behavior (β=0·031, OR=1·08). Schizophrenia PRS also predicted social and behavioural impairments as early as age 4 years. Interpretation. Childhood cognitive, social, behavioral and emotional impairments, implicated as antecedents to schizophrenia in high-risk, developmental studies, may represent early manifestations of genetic liability. Funding. This work was supported by the Medical Research Council (MR/M012964/1)