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The genetic architectures of functional and structural connectivity properties within cerebral resting-state networks

Publication year 2023
Published in eNeuro
Authors Elleke Tissink, Josefin Werme, Siemon De Lange, Jeanne E Savage, Yongbin Wei, Christiaan A de Leeuw, Mats Nagel, Danielle Posthuma, Martijn P van den Heuvel

Functional connectivity within resting-state networks (RSN-FC) is vital for cognitive functioning. RSN-FC is heritable and partially translates to the anatomical architecture of white matter, but the genetic component of structural connections of RSNs (RSN-SC) and their potential genetic overlap with RSN-FC remain unknown. Here we perform genome-wide association studies (Ndiscovery=24,336; Nreplication=3,412) and annotation on RSN-SC and RSN-FC. We identify genes for visual network-SC that are involved in axon guidance and synaptic functioning. Genetic variation in RSN-FC impacts biological processes relevant to brain disorders that previously were only phenotypically associated with RSN-FC alterations. Correlations of the genetic components of RSNs are mostly observed within the functional domain, whereas less overlap is observed within the structural domain and between the functional and structural domains. This study advances the understanding of the complex functional organization of the brain and its structural underpinnings from a genetics viewpoint.Significance StatementBrain regions with synchronized activity can be clustered into distinct networks. We investigate which genetic effects contribute to structural and functional connectivity within seven networks and assess their degree of shared genetic signal. Multiple genetic effects are identified and highlight relevant biological processes for brain connectivity and brain disorders related to the networks. Overlap between the genetics of network connectivity is mostly observed within the functional domain. These results advance our biological understanding of the complex functional organisation of the brain and its structural underpinnings, and their relevance for the genetics of neuropsychiatry.

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