Brain wiring economics, network organisation and population-level genomics

What role do our genes play in shaping the structural organisation of the living human brain? Across a sample of 2,153 children (9-11 years old), we address this question, focusing on common genetic variants associated with cognitive ability and diffusion-based structural neuroimaging. Using polygenic scores, we test how variability in the genetic signal associated with cognitive ability is linked to simulated structural network properties, such as network efficiency. We fit a computational model to each connectome that simulates the emergence of high-level network properties. Central to the model is an economic trade-off between the "cost" of forming a given connection (a distance penalty) and the topological "value" that connection brings to the network. To simulate the network properties of those with the highest genetic propensity for cognitive ability, we had to use a significantly weakerwiring costpenalty. This softer distance penalty produces more stochastic, diverse, and efficient simulated networks. Further, those with a high genetic propensity for cognitive ability exhibited a more randomised simulated topology. Finally, we took a different approach to exploring the relationships between genes and model parameters by linking thedistributionof those parameters with post-mortem gene expression data, with a comparative pathway enrichment analysis. Across the sample, overlapping biological and cellular pathways between polygenic scores and each child's optimal cost-value trade-off emerged. Together, the generative wiring distance term, which varied maximally across participants but minimally across the cortex, was enriched for more ontologies than the wiring value term, which varied maximally across the cortex. However, the overlap in enriched ontologies between polygenic scores and the wiringvalueterm was greater than that of polygenic scores and the wiringdistanceterm. This application of computational modelling demonstrates that the underlying economic trade-offs needed to simulate the higher-order topological properties of networks vary according to genetic propensity for cognitive ability.