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Association between gene expression and altered resting-state functional networks in type 2 diabetes
Yang Zhang1, Xin Du1, Wen Qin1
1Department of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
Background:
Type 2 diabetes (T2DM) is a polygenic metabolic disorder that accelerates brain aging and harms cognitive function. The underlying mechanism of T2DM-related brain functional changes has not been clarified.
Methods:
Resting-fMRI data were obtained from 99 T2DM and 109 healthy controls (HCs). Resting-state functional connectivity networks (RSNs) were separated using the Independent Component Analysis (ICA) method, and functional connectivity (FC) differences between T2DM patients and HCs within the RSNs were detected. A partial least squares (PLS) regression was used to test the relation between gene expression from Allen Human Brain Atlas (AHBA) and intergroup FC differences within RSNs. Then the FC differences-related gene sets were enriched to determine the biological processes and pathways related to T2DM brain FC changes.
Result:
The T2DM patients showed significantly increased FC in the left middle occipital gyrus (MOG) of the precuneus network (PCUN) and the right MOG / right precuneus of the dorsal attention network (DAN). FC differences within the PCUN were linked with the expression of genes enriched in the potassium channel and TrkB-Rac1 signaling pathways and biological processes related to synaptic function.
Conclusion:
This study linked FC and molecular alterations related to T2DM and suggested that the T2DM-related brain FC changes may have a genetic basis. This study hoped to provide a unique perspective to understand the biological substrates of T2DM-related brain changes.
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