The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan
- University of Oslo, Norway
- University of Barcelona, Spain
- Max Planck Institute for Human Development, Germany
- VA San Diego Healthcare System, United States
- University of California, San Diego, United States
- Norwegian University of Science and Technology, Norway
- University of Cambridge, United Kingdom
- MRC Cognition and Brain Sciences Unit, United Kingdom
- Umeå University, Sweden
- Faculty of Medicine, University of Barcelona, Spain
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 38127 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.
Data availability
The following is included in a separate section in the manuscript:Data availabilityThe study comprises many different data sources. The PI does not have the legal right to share these data directly. UK Biobank data can be obtained from www.ukbiobank.ac.uk. The data repository for the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) dataset can be found at www.cam-can.org/index.php?content=dataset. Access to BASE-II data can be obtained at www.base2.mpg.de/7549/data-documentation. Access to VETSA data can be obtained at https://medschool.ucsd.edu/som/psychiatry/research/VETSA/Researchers/Pages/default.aspx. Betula is described at www.umu.se/en/research/projects/betula---aging-memory-and-dementia/. For data from Barcelona brain studies, see www.neurociencies.ub.edu/david-bartres-faz/. For LCBC Lifespan sample, contact information can be found at https://www.oslobrains.no/presentation/anders-m-fjell/. Part of the developmental sample can be accessed through https://www.fhi.no/en/studies/moba/for-forskere-artikler/research-and-data-access/ (As of 2021, we are in the process of transferring MRI data to this repository). Please note that for all samples, data transfer agreements must be signed and proper ethical and data protection approvals must be in place, according to national legislation. Code used for data analysis accompany the submission as separate files. The correlation matrices constituting the basis for the Mantel tests are also uploaded.
Article and author information
Author details
Anders Martin Fjell
Andreas M Brandmaier
Rogier Andrew Kievit
Ulman Lindenberger
Athanasia Monika Mowinckel
Funding
European Research Council (283634;725025;313440)
- Anders Martin Fjell
- Kristine Beate Walhovd
the Medical Research Council Cognition & Brain Sciences Unit
- Rogier Andrew Kievit
U.S. National Institute on Aging (AG022381,AG050595)
- William S Kremen
EU Horizon 2020 (732592)
- Kristine Beate Walhovd
Knut and Alice Wallenberg foundation
- Lars Nyberg
Norwegian Research Council
- Anders Martin Fjell
- Kristine Beate Walhovd
Spanish Ministry of Science, Innovation and Universities
- David Bartres-Faz
the California Walnut Commission (NCT01634841)
- David Bartres-Faz
German Federal Ministry of Education and Research (16SV5537/16SV5837/16SV5538/16SV5536K/01UW0808/01UW0706/01GL1716A/01GL1716B)
- Ulman Lindenberger
European Research Council (677804)
- Simone Kühn
Biotechnology and Biological Sciences Research Council
- Rogier Andrew Kievit
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The studies were approved by the Norwegian Regional Committee for Medical and Health Research Ethics South. Written informed consent was obtained from all participants older than 12 years of age and from a parent/guardian of volunteers under 16 years of age. Oral informed consent was obtained from all participants under 12 years of age. Non-Norwegian samples were approved by the relevant ethical review board for each country. Norway (2010/2359; 2010/3407; 2009/200)
Reviewing Editor
- Alex Fornito, Monash University, Australia
Version history
- Received: January 12, 2021
- Accepted: June 26, 2021
- Accepted Manuscript published: June 28, 2021 (version 1)
- Version of Record published: July 6, 2021 (version 2)
Copyright
© 2021, Fjell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan
eLife 10:e66466.
https://doi.org/10.7554/eLife.66466
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