MIR137polygenic risk is associated with schizophrenia and affects functional connectivity of the dorsolateral prefrontal cortex
MIR137polygenic risk is associated with schizophrenia and affects functional connectivity of the dorsolateral prefrontal cortex
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MIR137多基因风险与精神分裂症相关，并影响背外侧前额皮质的功能连接
DOI：
10.1017/s0033291719001442
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发表时间：
2020-07-01
影响因子：
6.9
通讯作者：
Liu, Bing
中科院分区：
文献类型：
--
作者：
Liu, Shu;Li, Ang;Liu, Bing
背景全基因组关联研究（GWAS）一致显示microRNA 137（MIR137）的变体与精神分裂症有相当显著的关联。识别MIR137调节的基因网络可以为了解精神分裂症的生物学过程提供见解。此外，DLPFC功能连接，一个强大的相关MIR137，可能提供合理的内表型。然而，MIR137基因网络在功能连接中断中的调节作用仍不清楚。在这里，我们测试了MIR137调节基因对精神分裂症风险和DLPFC功能连接的影响。方法采用MIR137多基因风险评分（PRS）法，对589例精神分裂症患者和575例正常对照者的MIR137多基因风险评分进行了分析，以评价MIR137调控基因（N = 1274）的加性效应。然后，我们在两个独立的年轻健康队列（N= 356和N = 314）中研究了MIR137 PRS和DLPFC功能连接之间的关联。结果发现MIR137 PRS成功地捕捉到了患者和对照组之间的遗传结构差异，而单基因MIR137则没有。然后，我们一致发现，在两个独立的队列中，较高的MIR137 PRS与DLPFC与上级顶叶皮层和颞叶皮层之间的较低功能连接相关。结论DLPFC的这两种功能联系可能是MIR137调控的遗传结构与精神分裂症之间的重要内表型联系。
Background Genome-wide association studies (GWAS) have consistently revealed that a variant of microRNA 137 (MIR137) shows a quite significant association with schizophrenia. Identifying the network of genes regulated byMIR137could provide insights into the biological processes underlying schizophrenia. In addition, DLPFC functional connectivity, a robust correlate ofMIR137,may provide plausible endophenotypes. However, the regulatory role of theMIR137gene network in the disrupted functional connectivity remains unclear. Here, we tested the effects of theMIR137regulated genes on the risk for schizophrenia and DLPFC functional connectivity. Methods To evaluate the additive effects of theMIR137regulated genes (N= 1274), we calculated aMIR137polygenic risk score (PRS) for schizophrenia and tested its association with the risk for schizophrenia in the genomic data of a Han Chinese population that included schizophrenia patients (N= 589) and normal controls (N= 575). We then investigated the association betweenMIR137PRS and DLPFC functional connectivity in two independent young healthy cohorts (N= 356 andN= 314). Results We found that theMIR137PRS successfully captured the differences in genetic structure between the patients and controls, but the single geneMIR137did not. We then consistently found that a higherMIR137PRS was correlated with lower functional connectivities between the DLPFC and both the superior parietal cortex and the inferior temporal cortex in two independent cohorts. Conclusion The findings suggested that these two functional connectivities of the DLPFC could be important endophenotypes linking theMIR137-regulated genetic structure to schizophrenia.