Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-17051-5
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Funding
- Intramural Research Program of the National Institute of Mental Health
- Eunice Kennedy Shriver National Institute of Child Health [89-M-006, 08-CH-213]
- NIH Oxford-Cambridge Scholars' Program
- Gates Cambridge Trust
- Postdoctoral Fellowship from the British Academy
- Medical Research Council [MR/K020706/1]
- MQ: Transforming Mental Health [MQF17_24]
- Eunice Kennedy Shriver National Institute of Child Health (NIH) [1ZIAMH002949-02, ZIA MH002794-13, 1-ZIA-HD008898]
- EPSRC [EP/N510129/1]
- Henslow Fellowship at Lucy Cavendish College, University of Cambridge
- Cambridge Philosophical Society
- NIH Bench-to-Bedside grant
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002949] Funding Source: NIH RePORTER
- MRC [MC_G0802534, MR/K020706/1] Funding Source: UKRI
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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. How neurodevelopmental disorder-associated risk genes are translated into spatially patterned brain vulnerabilities is unclear. Here, the authors show that disorder-specific patterns of neuroanatomical changes are aligned to brain expression maps of disease risk genes in healthy subjects.
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