Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders.
IF: 17.694
Cited by: 98


Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.


Spatial Gene Expression
Spatial Anatomic

MeSH terms

Brain Mapping
Cerebral Cortex
Cohort Studies
DNA Copy Number Variations
Gene Expression Profiling
Genetic Predisposition to Disease
Genome, Human
Magnetic Resonance Imaging
Middle Aged
Neurodevelopmental Disorders
Spatial Analysis
Young Adult


Seidlitz, Jakob
Nadig, Ajay
Liu, Siyuan
Bethlehem, Richard A I
Vértes, Petra E
Morgan, Sarah E
Váša, František
Romero-Garcia, Rafael
Lalonde, François M
Clasen, Liv S
Blumenthal, Jonathan D
Paquola, Casey
Bernhardt, Boris
Wagstyl, Konrad
Polioudakis, Damon
de la Torre-Ubieta, Luis
Geschwind, Daniel H
Han, Joan C
Lee, Nancy R
Murphy, Declan G
Bullmore, Edward T
Raznahan, Armin

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