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Functional connectome-wide associations of schizophrenia polygenic risk.
Molecular Psychiatry ( IF 11.0 ) Pub Date : 2020-03-03 , DOI: 10.1038/s41380-020-0699-3
Hengyi Cao 1 , Hang Zhou 2 , Tyrone D Cannon 1, 2
Affiliation  

Schizophrenia is a highly heritable mental disorder characterized by functional dysconnectivity across the brain. However, the relationships between polygenic risk factors and connectome-wide neural mechanisms are unclear. Here, combining genetic and multiparadigm fMRI data of 623 healthy Caucasian adults drawn from the Human Connectome Project, we found that higher schizophrenia polygenic risk scores were significantly correlated with lower functional connectivity in a large-scale brain network primarily encompassing the visual system, default-mode system, and frontoparietal system. Such correlation was robustly observed across multiple fMRI paradigms, suggesting a brain-state-independent neural phenotype underlying individual genetic liability to schizophrenia. Moreover, using an independent clinical dataset acquired from the Consortium for Neuropsychiatric Phenomics, we further demonstrated that the connectivity of the identified network was reduced in patients with schizophrenia and significantly correlated with general cognitive ability. These findings provide the first evidence for connectome-wide associations of schizophrenia polygenic risk at the systems level and suggest that disrupted integration of sensori-cognitive information may be a hallmark of genetic effects on the brain that contributes to the pathogenesis of schizophrenia.

中文翻译:

精神分裂症多基因风险的功能性全连接组关联。

精神分裂症是一种高度遗传的精神障碍,其特征是整个大脑的功能性连接障碍。然而,多基因风险因素与连接组范围内的神经机制之间的关系尚不清楚。在这里,结合来自人类连接组计划的 623 名健康白人成年人的遗传和多范式 fMRI 数据,我们发现较高的精神分裂症多基因风险评分与主要包含视觉系统的大规模脑网络中较低的功能连通性显着相关,默认-模式系统和额顶叶系统。这种相关性在多个 fMRI 范式中得到了强有力的观察,表明个体对精神分裂症的遗传易感性与大脑状态无关的神经表型。而且,使用从神经精神现象学联合会获得的独立临床数据集,我们进一步证明了精神分裂症患者已识别网络的连通性降低,并且与一般认知能力显着相关。这些发现首次提供了系统水平上精神分裂症多基因风险的全连接组关联的证据,并表明感觉认知信息的整合中断可能是导致精神分裂症发病机制的大脑遗传效应的标志。
更新日期:2020-04-24
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