Association between polygenic risk for schizophrenia, neurocognition and social cognition across development.
Association between polygenic risk for schizophrenia, neurocognition and social cognition across development.
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DOI：
10.1038/tp.2016.147
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发表时间：
2016-10-18
影响因子：
6.8
通讯作者：
Gur RE
中科院分区：
文献类型：
--
作者：
Germine L;Robinson EB;Smoller JW;Calkins ME;Moore TM;Hakonarson H;Daly MJ;Lee PH;Holmes AJ;Buckner RL;Gur RC;Gur RE
突破性基因组学已经开始解开精神分裂症风险的遗传结构，提供了基于常见遗传变异的精神分裂症多基因风险量化方法。本研究的目的是了解精神分裂症遗传风险变异与健康个体神经认知发育之间的关系。我们首先使用费城神经发育队列（4303名8-21岁的参与者）的基因组和神经认知数据，筛选26种神经认知表型与精神分裂症多基因风险的相关性。根据最近的精神分裂症全基因组关联分析的汇总统计量，估计了每名受试者的精神分裂症多基因风险（精神病学基因组学联盟2014）。经多重比较校正后，精神分裂症多基因风险与情感识别和言语推理速度降低显著相关。这些协会是显着的9岁，没有证据表明精神分裂症多基因风险和年龄之间的相互作用对神经认知性能。然后，我们在哈佛/MGH脑基因组学超级结构项目样本（695名年龄在18-35岁之间的参与者）中研究了精神分裂症多基因风险与情绪识别速度之间的关联，在那里我们复制了精神分裂症多基因风险与情绪识别速度之间的关联。这些分析为精神分裂症的多基因风险与社会认知的特定方面之间的可复制关联提供了证据。我们的研究结果表明，精神分裂症遗传风险的个体差异与社会认知和潜在的言语推理方面的发展有关，并且这些关联在发展中相对较早出现。
Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8–21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18–35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development.