4.8 Article

Genetic influences on hub connectivity of the human connectome

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-021-24306-2

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Funding

  1. MASSIVE HPC facility
  2. Sylvia and Charles Viertel Charitable Foundation
  3. NIH Institutes and Centers [1U54MH091657]
  4. McDonnell Center for Systems Neuroscience at Washington University

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The study shows that genes play a significant and preferential role in influencing the strength of connections between brain network hubs, which are characterized by high metabolic costs.
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 magnetic resonance imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs. How genes sculpt the complex architecture of the human connectome remains unclear. Here, the authors show that genes preferentially influence the strength of connectivity between functionally valuable, metabolically costly connections between brain network hubs.

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