Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

Jakob Seidlitz (), Ajay Nadig, Siyuan Liu, Richard A. I. Bethlehem, Petra E. Vértes, Sarah E. Morgan, František Váša, Rafael Romero-Garcia, François M. Lalonde, Liv S. Clasen, Jonathan D. Blumenthal, Casey Paquola, Boris Bernhardt, Konrad Wagstyl, Damon Polioudakis, Luis Torre-Ubieta, Daniel H. Geschwind, Joan C. Han, Nancy R. Lee, Declan G. Murphy, Edward T. Bullmore and Armin Raznahan ()
Additional contact information
Jakob Seidlitz: National Institute of Mental Health
Ajay Nadig: National Institute of Mental Health
Siyuan Liu: National Institute of Mental Health
Richard A. I. Bethlehem: University of Cambridge
Petra E. Vértes: University of Cambridge
Sarah E. Morgan: University of Cambridge
František Váša: University of Cambridge
Rafael Romero-Garcia: University of Cambridge
François M. Lalonde: National Institute of Mental Health
Liv S. Clasen: National Institute of Mental Health
Jonathan D. Blumenthal: National Institute of Mental Health
Casey Paquola: Montreal Neurological Institute and Hospital
Boris Bernhardt: Montreal Neurological Institute and Hospital
Konrad Wagstyl: University of Cambridge
Damon Polioudakis: Semel Institute, David Geffen School of Medicine, UCLA
Luis Torre-Ubieta: Semel Institute, David Geffen School of Medicine, UCLA
Daniel H. Geschwind: Semel Institute, David Geffen School of Medicine, UCLA
Joan C. Han: University of Tennessee Health Science Center and Le Bonheur Children’s Foundation Research Institute
Nancy R. Lee: Drexel University
Declan G. Murphy: King’s College London
Edward T. Bullmore: University of Cambridge
Armin Raznahan: National Institute of Mental Health

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17051-5

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DOI: 10.1038/s41467-020-17051-5

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