Lucy Riglin1, Stephan Collishaw1, Alexander Richards1, Ajay K Thapar1, Barbara Maughan2, Michael C O'Donovan1, Anita Thapar3. 1. Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. 2. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Kings College London, London, UK. 3. Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. Electronic address: thapar@cardiff.ac.uk.
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.
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.
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