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

eLife

Jeremy Elman¹  Carol E Franz¹  William S Kremen²  Matthew S Panizzon³  Yunpeng Wang⁴  Stine K Krogsrud⁴  Inge K Amlien⁴  Athanasia Monika Mowinckel⁴  Øystein Sørensen⁴  Hakon Grydeland⁴  Rene Westerhausen⁴  Lars Nyberg⁵  Kristine Beate Walhovd⁶  Anders Martin Fjell⁶  Sandra Düzel⁷  Simone Kühn⁸  Andreas M Brandmaier⁹  Ulman Lindenberger⁹  Cristina Solé-Padullés^1,10  David Bartres-Faz^1,10  Didac Macía^1,10  Asta K Håberg^1,11  Rogier Andrew Kievit^1,12  Tim C Kietzmann^1,13 

[1] Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, United States;Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, United States;Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, United States;Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, United States;Department of Psychiatry, University of California, San Diego, La Jolla, United States;Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway;Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway;Department of Radiation Sciences, Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden;Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway;Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway;Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany;Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany;Lise Meitner Group for Environmental Neuroscience, Max Planck Institute for Human Development, Berlin, Germany;Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany;Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany;Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, and Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain;Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway;Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom;MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom;Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands;

关键词: lifespan;    genetics;    brain;    Human;   

DOI  :  10.7554/eLife.66466

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY