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Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

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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 de la Torre-Ubieta, Daniel H. Geschwind, Joan C. Han, Nancy R. Lee, Declan G. Murphy & 2 more Edward T. Bullmore, Armin Raznahan

Original languageEnglish
Article number3358
Number of pages14
JournalNature Communications
Volume11
Issue number1
Early online date3 Jul 2020
DOIs
Accepted/In press11 May 2020
E-pub ahead of print3 Jul 2020
Published3 Jul 2020

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King's Authors

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.

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