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The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan

Published version
Peer-reviewed

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Authors

Fjell, Anders Martin  ORCID logo  https://orcid.org/0000-0003-2502-8774
Grydeland, Hakon 
Wang, Yunpeng 
Amlien, Inge K 

Abstract

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume–volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

Description

Funder: Knut and Alice Wallenberg Foundation; FundRef: http://dx.doi.org/10.13039/501100004063


Funder: Norwegian Research Council; FundRef: http://dx.doi.org/10.13039/501100005416


Funder: Biotechnology and Biological Sciences Research Council; FundRef: http://dx.doi.org/10.13039/501100000268


Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265

Keywords

Research Article, Neuroscience, lifespan, genetics, brain, Human

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X

Volume Title

10

Publisher

eLife Sciences Publications, Ltd
Sponsorship
European Research Council (283634)
Horizon 2020 (732592)
Spanish Ministry of Science and Innovation (MICIU/FEDER/RTI2018-095181-B-C21)
California Walnut Commission (NCT01634841)
Federal Ministry of Education and Research (16SV5537/16SV5837/16SV5538/16SV5536K/01UW0808/01UW0706/01GL1716A/01GL1716B)
European Research Council (677804)
U.S. National Institute on Aging (AG022381)
European Research Council (725025)
European Research Council (313440)
U.S. National Institute on Aging (AG050595)
Institució Catalana de Recerca i Estudis Avançats (ICREA Academia-2019)