Genetic influences on hub connectivity of the human connectome.
Aurina ArnatkeviciuteBen D FulcherStuart OldhamJeggan TiegoCasey PaquolaZachary F GerringKevin AquinoZiarih HawiBeth JohnsonGareth BallMarieke KleinGustavo DecoBarbara FrankeMark A BellgroveSidhant ChopraPublished in: Nature communications (2021)
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.
Keyphrases
- resting state
- functional connectivity
- genome wide
- endothelial cells
- diffusion weighted
- white matter
- bioinformatics analysis
- induced pluripotent stem cells
- single cell
- pluripotent stem cells
- gene expression
- contrast enhanced
- copy number
- network analysis
- blood brain barrier
- electronic health record
- magnetic resonance imaging
- big data
- multiple sclerosis
- oxidative stress
- genome wide analysis
- room temperature
- brain injury