Genome-wide association study of brain functional and structural networks

Imaging genetics studies with large samples have identified many genes associated with brain functions and structures, but little is known about genes associated with brain functional and structural network properties. The current genome-wide association study examined graph theory measures of brain structural and functional networks with 497 healthy Chinese participants (17-28 years). Four genes (TGFB3, LGI1, TSPAN18, and FAM155A) were identified to be significantly associated with functional network global efficiency, and two (NLRP6 and ICE2) with structural network global efficiency. Meta-analysis of structural and functional brain network property confirmed the four functional-related genes and revealed two more (RBFOX1 and WWOX). They were reported to be significantly associated with regional brain structural or functional measurements in the UK Biobank project; and showed differential gene expression level between low and high structure-function coupling regions according to Allen Human Brain Atlas gene expression data. Taken together, our results suggest that brain structural and functional networks had shared and unique genetic bases, consistent with the notion of many-to-many structure-function coupling of the brain. Genome-wide association studies on brain were often conducted with regional measurements of the brain (e.g., regional volume, thickness) rather than whole-brain properties. Here we associated whole genome to whole-brain structural and functional network properties (global efficiency, local efficiency, small-worldness), and identified four genes (TGFB3, LGI1, TSPAN18, and FAM155A) associated with functional brain network and two genes (NLRP6 and ICE2) with structural network. Two more genes (RBFOX1 and WWOX) were identified by meta-analysis. These genes were reported to be associated with brain regional measurements in the UK Biobank project, and they showed differential gene expression level between low and high structure-function coupling regions, suggesting shared and unique genetic bases for functional and structural brain networks.