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Specificity and overlap in the genetic architectures of functional and structural connectivity within cerebral resting-state networks

Tissink, E.; Werme, J.; de Lange, S. C.; Savage, J. E.; Wei, Y.; de Leeuw, C. A.; Nagel, M.; Posthuma, D.; van den Heuvel, M. P.

2022-05-31 genetics
10.1101/2022.05.31.494125 bioRxiv
Show abstract

The functional connectivity and dynamics of resting-state networks (RSN-FC) are 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 remains unknown. Here we perform genome-wide association studies (Ndiscovery=24,336; Nreplication=3,412) and in silico annotation on RSN-SC and RSN-FC. We identify the first genes for visual network-SC, that are involved in axon guidance and synaptic functioning and show that genetic variation in RSN-FC impacts biological processes related to brain disorders that have previously been associated with FC alterations in those same RSNs. 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.

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