Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.

To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.

A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored.

There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.

The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.

精神分裂症被认为是一种多基因疾病。精神分裂症患者和遗传性精神分裂症高风险 (GHR) 患者在大脑半球不对称方面表现出类似的神经发育缺陷。精神分裂症和 GHR 患者的神经发育异常和精神分裂症相关风险基因之间的潜在关联仍不清楚。

调查精神分裂症患者和 GHR 患者结构网络的共同和特定变化。并确定易受攻击的结构网络交替与精神分裂症相关风险基因之间的关联。

共有 97 名精神分裂症患者、79 名 GHR 患者和 192 名健康对照者在单个部位接受了弥散张量成像 (DTI) 扫描。我们使用图论来表征半球和全脑结构网络拓扑度量。对于精神分裂症组的 26 人和 GHR 组的 48 人进行 DTI 扫描，我们还计算了他们的精神分裂症相关多基因风险评分 (SZ-PRS)。计算了结构网络变化与 SZ-PRS 之间的相关性。基于确定的遗传-神经关联，探索了生物信息学的富集。

精神分裂症和 GHR 组的节点效率、全局和局部效率存在显着的半球不对称缺陷。在精神分裂症和 GHR 组中，局部效率的半球不对称缺陷与 SZ-PRS 显着正相关。生物信息学富集分析表明，这些风险基因可能与信号转导、神经发育和神经元结构有关。精神分裂症组表现出全脑结构网络显着下降。

精神分裂症患者和 GHR 患者的共同不对称缺陷，以及异常不对称与 SZ-PRS 之间的关联表明，易感性成像标记物受精神分裂症相关风险基因调控。我们的研究结果为风险基因调控的不对称性提供了新的见解，并提供了对精神分裂症的遗传-神经病理学基础的更好理解。