TY - JOUR
T1 - Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders
AU - Seidlitz, Jakob
AU - Nadig, Ajay
AU - Liu, Siyuan
AU - Bethlehem, Richard A.I.
AU - Vértes, Petra E.
AU - Morgan, Sarah E.
AU - Váša, František
AU - Romero-Garcia, Rafael
AU - Lalonde, François M.
AU - Clasen, Liv S.
AU - Blumenthal, Jonathan D.
AU - Paquola, Casey
AU - Bernhardt, Boris
AU - Wagstyl, Konrad
AU - Polioudakis, Damon
AU - de la Torre-Ubieta, Luis
AU - Geschwind, Daniel H.
AU - Han, Joan C.
AU - Lee, Nancy R.
AU - Murphy, Declan G.
AU - Bullmore, Edward T.
AU - Raznahan, Armin
AU - Morgan, Sarah
PY - 2020/7/3
Y1 - 2020/7/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85087425878&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17051-5
DO - 10.1038/s41467-020-17051-5
M3 - Article
C2 - 32620757
AN - SCOPUS:85087425878
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3358
ER -