The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

Elleke Tissink; Josefin Werme; Siemon C. de Lange; Jeanne E. Savage; Yongbin Wei; Christiaan A. de Leeuw; Mats Nagel; Danielle Posthuma; Martijn P. van den Heuvel

doi:10.1523/ENEURO.0242-22.2023

The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

Elleke Tissink, Josefin Werme, Siemon C. de Lange, Jeanne E. Savage, Yongbin Wei, Christiaan A. de Leeuw, Mats Nagel, Danielle Posthuma, Martijn P. van den Heuvel^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Functional connectivity within resting-state networks (RSN-FC) is vital for cognitive functioning. RSN-FC is her-itable and partially translates to the anatomic 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 (N_discovery = 24,336; N_replication = 3412) 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 previ-ously 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.

Original language	English
Article number	ENEURO.0242-22.2023
Pages (from-to)	1-16
Number of pages	16
Journal	eNeuro
Volume	10
Issue number	4
Early online date	7 Mar 2023
DOIs	https://doi.org/10.1523/ENEURO.0242-22.2023
Publication status	Published - Apr 2023

Bibliographical note

Funding Information:
D.P. was supported by The Netherlands Organization for Scientific Research (NWO) Grant VICI 453-14-005, the NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology Grant No. 024.004.012, and the European Research Council (ERC) Advanced Grant No. ERC-2018-AdG GWAS2FUNC 834057. The work of S.C.d.L. was supported by the ZonMw Open Competition Project REMOVE 09120011910032. C.A.d.L. is supported by Hoffman-La Roche. M.P.v.d.H. was supported by NWO VIDI Grant 452-16-015 and the ERC Consolidator of the European Research Council Grant 101001062. J.E.S. was supported by the NWO VENI Grant 201G-064.

Publisher Copyright:
© 2023 Tissink et al.

Funding

D.P. was supported by The Netherlands Organization for Scientific Research (NWO) Grant VICI 453-14-005, the NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology Grant No. 024.004.012, and the European Research Council (ERC) Advanced Grant No. ERC-2018-AdG GWAS2FUNC 834057. The work of S.C.d.L. was supported by the ZonMw Open Competition Project REMOVE 09120011910032. C.A.d.L. is supported by Hoffman-La Roche. M.P.v.d.H. was supported by NWO VIDI Grant 452-16-015 and the ERC Consolidator of the European Research Council Grant 101001062. J.E.S. was supported by the NWO VENI Grant 201G-064.

Funders	Funder number
ZonMw Open Competition	09120011910032
F. Hoffmann-La Roche	201G-064, 101001062, 452-16-015
F. Hoffmann-La Roche
European Research Council	ERC-2018-AdG GWAS2FUNC 834057
European Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.004.012, VICI 453-14-005
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

connectivity
GWAS
networks
neuroimaging
resting-state
structure-function

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title = "The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks",

abstract = "Functional connectivity within resting-state networks (RSN-FC) is vital for cognitive functioning. RSN-FC is her-itable and partially translates to the anatomic 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 = 3412) 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 previ-ously 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.",

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AU - Savage, Jeanne E.

AU - Wei, Yongbin

AU - de Leeuw, Christiaan A.

AU - Nagel, Mats

AU - Posthuma, Danielle

AU - van den Heuvel, Martijn P.

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The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

Abstract

Bibliographical note

Funding

Keywords

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