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

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• 作者：Lucy Riglin ; PhD^a ; Stephan Collishaw ; PhD^a ; Alexander Richards ; PhD^a ; Ajay K Thapar ; MRCGP^a ; Prof Barbara Maughan ; PhD^b ; Prof Michael C O'Donovan ; FRCPsych^a ; Prof Anita Thapar ; FRCPsych^a ; ^{thapar@cardiff.ac.uk}
• 刊名：The Lancet Psychiatry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：4
• 期：1
• 页码：57-62
• 全文大小：84 K
• 卷排序：4

文摘

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.MethodsThe 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).FindingsAt 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.InterpretationChildhood cognitive, social, behavioural, and emotional impairments, implicated as antecedents to schizophrenia in high-risk, developmental studies, might represent early manifestations of genetic liability.FundingMedical Research Council.