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

  1. Anders Martin Fjell  Is a corresponding author
  2. Hakon Grydeland
  3. Yunpeng Wang
  4. Inge K Amlien
  5. David Bartres-Faz
  6. Andreas M Brandmaier
  7. Sandra Düzel
  8. Jeremy Elman
  9. Carol E Franz
  10. Asta K Håberg
  11. Tim C Kietzmann
  12. Rogier Andrew Kievit
  13. William S Kremen
  14. Stine K Krogsrud
  15. Simone Kühn
  16. Ulman Lindenberger
  17. Didac Macía
  18. Athanasia Monika Mowinckel
  19. Lars Nyberg
  20. Matthew S Panizzon
  21. Cristina Solé-Padullés
  22. Øystein Sørensen
  23. Rene Westerhausen
  24. Kristine Beate Walhovd
  1. University of Oslo, Norway
  2. University of Barcelona, Spain
  3. Max Planck Institute for Human Development, Germany
  4. VA San Diego Healthcare System, United States
  5. University of California, San Diego, United States
  6. Norwegian University of Science and Technology, Norway
  7. University of Cambridge, United Kingdom
  8. MRC Cognition and Brain Sciences Unit, United Kingdom
  9. Umeå University, Sweden
  10. 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.

The following previously published data sets were used

Article and author information

Author details

  1. Anders Martin Fjell

    Psychology, University of Oslo, Oslo, Norway
    For correspondence
    andersmf@psykologi.uio.no
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2502-8774
  2. Hakon Grydeland

    Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  3. Yunpeng Wang

    Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  4. Inge K Amlien

    Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  5. David Bartres-Faz

    Neuroscience, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Andreas M Brandmaier

    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8765-6982
  7. Sandra Düzel

    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Jeremy Elman

    Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Carol E Franz

    Department of Psychiatry, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Asta K Håberg

    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  11. Tim C Kietzmann

    MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Rogier Andrew Kievit

    MRC Cognition and Brain Sciences Unit, MRC Cognition and Brain Sciences Unit, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0700-4568
  13. William S Kremen

    MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Stine K Krogsrud

    Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  15. Simone Kühn

    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6823-7969
  16. Ulman Lindenberger

    Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Max Planck Institute for Human Development, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8428-6453
  17. Didac Macía

    Neuroscience, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  18. Athanasia Monika Mowinckel

    LCBC, Department of Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5756-0223
  19. Lars Nyberg

    Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3367-1746
  20. Matthew S Panizzon

    Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  21. Cristina Solé-Padullés

    Neuroscience, Faculty of Medicine, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  22. Øystein Sørensen

    Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  23. Rene Westerhausen

    Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  24. Kristine Beate Walhovd

    Department of Psychology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.

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

  1. Alex Fornito, Monash University, Australia

Publication history

  1. Received: January 12, 2021
  2. Accepted: June 26, 2021
  3. Accepted Manuscript published: June 28, 2021 (version 1)
  4. 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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  1. Anders Martin Fjell
  2. Hakon Grydeland
  3. Yunpeng Wang
  4. Inge K Amlien
  5. David Bartres-Faz
  6. Andreas M Brandmaier
  7. Sandra Düzel
  8. Jeremy Elman
  9. Carol E Franz
  10. Asta K Håberg
  11. Tim C Kietzmann
  12. Rogier Andrew Kievit
  13. William S Kremen
  14. Stine K Krogsrud
  15. Simone Kühn
  16. Ulman Lindenberger
  17. Didac Macía
  18. Athanasia Monika Mowinckel
  19. Lars Nyberg
  20. Matthew S Panizzon
  21. Cristina Solé-Padullés
  22. Øystein Sørensen
  23. Rene Westerhausen
  24. Kristine Beate Walhovd
(2021)
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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