Dissect Relationships Between Gene Co-expression and Functional Connectivity in Human Brain.

Xue Zhang,Bingbing Yang,Feng Liu,Zhaoxiang Ye,Peng Zhang,Yuan Ji,Chunshui Yu,Yingying Xie,Wei Li,Wen Qin,Jie Tang,Hao Ding

doi:10.3389/fnins.2021.797849

Abstract

Although recent evidence indicates an association between gene co-expression and functional connectivity in human brain, specific association patterns remain largely unknown. Here, using neuroimaging-based functional connectivity data of living brains and brain-wide gene expression data of postmortem brains, we performed comprehensive analyses to dissect relationships between gene co-expression and functional connectivity. We identified 125 connectivity-related genes (20 novel genes) enriched for dendrite extension, signaling pathway and schizophrenia, and 179 gene-related functional connections mainly connecting intra-network regions, especially homologous cortical regions. In addition, 51 genes were associated with connectivity in all brain functional networks and enriched for action potential and schizophrenia; in contrast, 51 genes showed network-specific modulatory effects and enriched for ion transportation. These results indicate that functional connectivity is unequally affected by gene expression, and connectivity-related genes with different biological functions are involved in connectivity modulation of different networks.

Highlights

Functional connectivity calculated from functional magnetic resonance imaging has been widely used to characterize intrinsic low-frequency synchronization of brain activity at rest between anatomically distinct brain regions (Ogawa et al, 1992)
In the 800 subjects, two sample t-test demonstrated that the global connectivity-expression coupling (CECs) values calculated based on the 1291 genes were greater (t = 11.00, P < 10−300) than those derived from the 10,185 genes (Figure 2E) and the population- and connectionaveraged Csa values of the 1291 genes were much stronger (t = 20.13; P < 10−300) than those of the 10,185 genes (Figure 2F)
We performed a comprehensive analysis on associations between functional connectivity and gene coexpression in the human brain

Summary

Introduction

Functional connectivity calculated from functional magnetic resonance imaging (fMRI) has been widely used to characterize intrinsic low-frequency synchronization of brain activity at rest between anatomically distinct brain regions (Ogawa et al, 1992). Regions and connections are organized into brain functional networks responsible for such distinct functions as vision, audition, motion, attention, memory, and emotion. Different combinations of connectivity impairments are indicative of different neuropsychiatric disorders, which are useful for diagnosing diseases, monitoring clinical courses, and predicting outcomes (Seeley et al, 2009; Vertes and Bullmore, 2015). Genome-wide association study (GWAS) is a putative method to identify genetic substrates of neuroimaging phenotypes, such as functional connectivity. Using a discovery dataset of 8428 subjects, a GWAS study has identified several genetic loci that are associated with a few functional

Methods

Results

Conclusion