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

Anders Martin Fjell , Hakon Grydeland, Yunpeng Wang, Inge K Amlien, David Bartres-Faz, Andreas M Brandmaier, Sandra Düzel, Jeremy Elman,  Carol E Franz, Asta K Håberg, Tim C Kietzmann, Rogier Andrew Kievit, William S Kremen, Stine K Krogsrud, Simone Kühn, Ulman Lindenberger, Didac Macía, Athanasia Monika Mowinckel, Lars Nyberg, Matthew S Panizzon, Cristina Solé-Padullés, Øystein Sørensen, Rene Westerhausen, Kristine Beate Walhovd

eLife 2021;10:e66466 DOI: 10.7554/eLife.66466


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.

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Published Aug. 16, 2021 1:41 PM - Last modified Aug. 19, 2021 10:09 AM