Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: a population-based cohort study
Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: a population-based cohort study
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DOI：
10.1016/s2215-0366(16)30406-0
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发表时间：
2017-01-01
影响因子：
64.3
通讯作者：
Thapar, Anita
中科院分区：
文献类型：
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作者：
Riglin, Lucy;Collishaw, Stephan;Thapar, Anita
精神分裂症通常在青春期后发病，但通常在可观察到的儿童神经发育障碍之前。这些童年前因是否反映了遗传倾向尚不清楚。我们使用来自患者发现样本的多基因风险评分作为精神分裂症遗传倾向性的指标。我们的目的是在英国以人口为基础的队列中确定这种责任的早期儿童表现。方法研究样本为Avon父母与儿童纵向研究，这是一项基于人群的前瞻性队列研究，涉及14701名儿童。数据主要采用基于回归的分析进行分析。多基因风险评分来自一项已发表的精神病学基因组学联盟全基因组关联研究。结果是儿童（4-9岁）四个发展领域的维度测量，包括12个指标：认知和学习、社会和沟通、情绪和情绪调节以及行为（n=5100-6952）。在7-9岁时，精神分裂症多基因风险评分与较低的表现智商（β -0.056, OR 1.13 [95% CI 1.04-1.23]）、较差的社会理解能力（β -0.032, OR 1.08[1.00-1.17]）、较差的语言可理解性和流畅性（β -0.032, OR 1.10[1.02-1.20]）、更易怒（β -0.032, OR 1.07[1.01-1.14]）和更任性的行为（β - 0.031, OR 1.08[1.02-1.15]）相关。精神分裂症多基因风险评分也可以预测早在4岁时的社会和行为障碍。在高风险的发育研究中，儿童认知、社会、行为和情感障碍被认为是精神分裂症的前因，可能是遗传倾向的早期表现。
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 scores 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.