Abstract
Mapping gene expression profiles to neuroimaging phenotypes in the same anatomical space provides opportunities to discover molecular substrates for human brain functional properties. Here, we aimed to identify cell-type-specific gene modules associated with the regional homogeneity (ReHo) of spontaneous brain activity and their associations with brain disorders. Fourteen gene modules were consistently associated with ReHo in the three datasets, five of which showed cell-type-specific expression (one neuron-endothelial module, one neuron module, one astrocyte module and two microglial modules) in two independent cell series of the human cerebral cortex. The neuron-endothelial module was mainly enriched for transporter complexes, the neuron module for the synaptic membrane, the astrocyte module for amino acid metabolism, and microglial modules for leukocyte activation and ribose phosphate biosynthesis. In enrichment analyses of cell-type-specific modules for 10 common brain disorders, only the microglial module was significantly enriched for genes obtained from genome-wide association studies of multiple sclerosis (MS) and Alzheimer’s disease (AD). The ReHo of spontaneous brain activity is associated with the gene expression profiles of neurons, astrocytes, microglia and endothelial cells. The microglia-related genes associated with MS and AD may provide possible molecular substrates for ReHo abnormality in both brain disorders.
Highlights
Resting-state functional magnetic resonance imaging has been widely used to assess spontaneous brain activity, which records the blood oxygen level-dependent (BOLD) fluctuations during rest
The neuron-endothelial module was enriched for transporter complexes, the neuron module for the synaptic membrane, the astrocyte module for amino acid metabolism, and the microglial modules for leukocyte activation and ribose phosphate anabolism, indicating that neurons, astrocytes, microglia and endothelial cells are all associated with the regional homogeneity (ReHo) of spontaneous brain activity
The higher expression of the brown module related to transporter complexes and ligand-activated transcription factor activity corresponds to higher ReHo; the higher expression of the blue module related to the formation of the synaptic membrane, signal release, and passive transmembrane transporter activity corresponds to lower ReHo
Summary
Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to assess spontaneous brain activity, which records the blood oxygen level-dependent (BOLD) fluctuations during rest. Regional homogeneity (ReHo) is a measure reflecting the degree of local synchronization that occurs over the course of the rs-fMRI, that is, the similarity of the fluctuation of BOLD signals of a given voxel with those of its nearest neighbors (Zang et al, 2004; Zuo et al, 2013), which is measured by Kendall’s coefficient of concordance (KCC). Candidate gene studies in healthy and diseased populations have indicated the genetic bases of ReHo (Yu et al, 2014; Zheng et al, 2017; Gou et al, 2018; Shang et al, 2019), the molecular substrates underlying the ReHo of spontaneous brain activity remain elusive
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