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MIR137 polygenic risk is associated with schizophrenia and affects functional connectivity of the dorsolateral prefrontal cortex

Published online by Cambridge University Press:  26 June 2019

Shu Liu ,
Ang Li ,
Yong Liu ,
Jin Li ,
Meng Wang ,
Yuqing Sun ,
Wen Qin ,
Chunshui Yu ,
Tianzi Jiang  and
Bing Liu Open the ORCID record for Bing Liu [Opens in a new window]
Shu Liu
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China
Ang Li
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China
Yong Liu
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China
Jin Li
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China
Meng Wang
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China
Yuqing Sun
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China
Wen Qin
Affiliation:
Department of Radiology, Tianjin Medical University General Hospital, Tianjin300052, China
Chunshui Yu
Affiliation:
Department of Radiology, Tianjin Medical University General Hospital, Tianjin300052, China
Tianzi Jiang
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu610054, China Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
Bing Liu*
Affiliation:
Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China University of Chinese Academy of Sciences, Beijing100049, China CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing100190, China
*
Author for correspondence: Bing Liu, E-mail: bliu@nlpr.ia.ac.cn
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Abstract

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 by MIR137 could provide insights into the biological processes underlying schizophrenia. In addition, DLPFC functional connectivity, a robust correlate of MIR137, may provide plausible endophenotypes. However, the regulatory role of the MIR137 gene network in the disrupted functional connectivity remains unclear. Here, we tested the effects of the MIR137 regulated genes on the risk for schizophrenia and DLPFC functional connectivity.

Methods

To evaluate the additive effects of the MIR137 regulated genes (N = 1274), we calculated a MIR137 polygenic 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 between MIR137 PRS and DLPFC functional connectivity in two independent young healthy cohorts (N = 356 and N = 314).

Results

We found that the MIR137 PRS successfully captured the differences in genetic structure between the patients and controls, but the single gene MIR137 did not. We then consistently found that a higher MIR137 PRS 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 the MIR137-regulated genetic structure to schizophrenia.

Keywords

Dorsolateral prefrontal cortexfunctional connectivitymicroRNA-137polygenic risk scoreschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 9 , July 2020 , pp. 1510 - 1518
Copyright
Copyright © Cambridge University Press 2019

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