The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence
The p factor: genetic analyses support a general dimension of psychopathology in childhood and adolescence
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DOI：
10.1111/jcpp.13113
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发表时间：
2019-09-20
影响因子：
7.6
通讯作者：
Plomin, Robert
中科院分区：
文献类型：
--
作者：
Allegrini, Andrea G.;Cheesman, Rosa;Plomin, Robert
背景儿童时期不同的行为问题与表型相关，这表明精神病理学的一个一般维度被称为p因素。儿童精神病理学特征之间的共同遗传结构也支持遗传p。本研究系统地调查了这一共同维度在儿童和青春期通过自我、父母和教师评定的措施的表现。方法样本包括7026对来自双胞胎早期发育研究(TEDS)的双胞胎。首先，我们使用多变量双胞胎模型，根据儿童、家长和教师在7岁、9岁、12岁和16岁时对行为问题(抑郁特征、情绪问题、同伴问题、自闭症特征、多动症、反社会行为、行为问题和精神变态倾向)的不同衡量标准，估计常见的遗传和环境影响。其次，为了评估遗传和环境影响在不同时间对p的稳定性，我们对四个年龄段的儿童精神病理学测量的第一个表型主成分进行了纵向双胞胎建模。第三，我们基于精神疾病的8个多基因得分，在7,026名无关的基因分型个体中创建了一个遗传p因子，以估计主要是成人精神障碍的一般多基因易感性与儿童p的关系。结果行为问题在不同年龄和评分者中一致地存在表型和遗传相关性。P因子基本上是可遗传的(50%-60%)，并且在不同的年龄和评分者中表现一致。然而，公共因素模型中的残差变化也表明了独特的贡献。儿童和青春期的p成分的遗传相关性表明，随着时间的推移，p成分的稳定性(49%-78%)。来自精神障碍研究的多基因一般精神病理学因素在整个发育过程中一致预测一般的表型p因素(0.3%-0.9%)。结论不同形式的精神病一般都有一个共同的p因子，具有很高的遗传性。儿童时期p的稳定性受遗传因素的影响很大。我们的分析表明，成年期精神障碍的一般风险与儿童时期的p之间存在遗传重叠，甚至在7岁时也是如此。p因素对基因组研究以及最终对行为问题的诊断和治疗具有深远的影响。
Background Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self-, parent- and teacher-rated measures in childhood and adolescence. Methods The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p. Results Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%-60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%-78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%-0.9%). Conclusions Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far-reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems.