Genetic influences on hub connectivity of the human connectome

Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted imaging in twins, we identify a major role for genes in shaping hub connectivity of the human connectome, showing that genes preferentially influence connectivity strength between network hubs. In two independent samples, we show that DNA variants preferentially related to hub connectivity are expression quantitative trait loci for genes that overlap with those implicated in intelligence, schizophrenia, and metabolism. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing thirteen generative models of network growth, we show that stochastic processes cannot explain the spatial distribution, and thus the precise wiring pattern, of hub connectivity. Together, our findings indicate that genetic influences on brain connectivity are not uniformly distributed throughout the brain, but are instead concentrated on the functionally valuable, metabolically costly connections between connectome hubs.