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

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Fjell, Anders Martin  ORCID logo
Grydeland, Hakon 
Wang, Yunpeng 
Amlien, Inge K 


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.



brain, genetics, human, lifespan, neuroscience, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Female, Humans, Longevity, Magnetic Resonance Imaging, Male, Middle Aged, Young Adult

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eLife Sciences Publications, Ltd
German Federal Ministry of Education and Research (16SV5537/16SV5837/16SV5538/16SV5536K/01UW0808/01UW0706/01GL1716A/01GL1716B)
EU Horizon 2020 (732592)
the California Walnut Commission (NCT01634841)
Institució Catalana de Recerca i Estudis Avançats (ICREA Academia-2019)
Federal Ministry of Education and Research (16SV5537/16SV5837/16SV5538/16SV5536K/01UW0808/01UW0706/01GL1716A/01GL1716B)
NIA NIH HHS (R01 AG022381, R01 AG050595)
California Walnut Commission (NCT01634841)
European Research Council (283634, 313440, 677804, 725025)
Spanish Ministry of Science and Innovation (MICIU/FEDER/RTI2018-095181-B-C21)
Horizon 2020 (732592)
U.S. National Institute on Aging (AG022381, AG050595)