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Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Nadig, Ajay 
Liu, Siyuan 
Bethlehem, Richard AI 
Vértes, Petra E 

Abstract

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.

Description

Keywords

Adolescent, Adult, Brain Mapping, Cerebral Cortex, Child, Cohort Studies, DNA Copy Number Variations, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome, Human, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurodevelopmental Disorders, Neuroimaging, Neurons, Oligodendroglia, Spatial Analysis, Young Adult

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Department of Health (via National Institute for Health Research (NIHR)) (156239)
Medical Research Council (MR/K020706/1)
British Academy (PFO\170517)
Guarantors of Brain (unknown)
MQ: Transforming Mental Health (MQ17-24 Vertes)
Medical Research Council (MC_G0802534)