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 de la Torre-Ubieta; Daniel H. Geschwind; Joan C. Han; Nancy R. Lee; Declan G. Murphy; Edward T. Bullmore; Armin Raznahan; Sarah Morgan

doi:10.1038/s41467-020-17051-5

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 de la Torre-Ubieta, Daniel H. Geschwind, Joan C. Han, Nancy R. Lee, Declan G. MurphyEdward T. Bullmore, Armin Raznahan, Sarah Morgan

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	3358
Number of pages	14
Journal	Nature Communications
Volume	11
Issue number	1
Early online date	3 Jul 2020
DOIs	https://doi.org/10.1038/s41467-020-17051-5
Publication status	Published - 3 Jul 2020

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Seidlitz, J., Nadig, A., Liu, S., Bethlehem, R. A. I., Vértes, P. E., Morgan, S. E., Váša, F., Romero-Garcia, R., Lalonde, F. M., Clasen, L. S., Blumenthal, J. D., Paquola, C., Bernhardt, B., Wagstyl, K., Polioudakis, D., de la Torre-Ubieta, L., Geschwind, D. H., Han, J. C., Lee, N. R., ... Morgan, S. (2020). Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders. Nature Communications, 11(1), Article 3358. https://doi.org/10.1038/s41467-020-17051-5

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title = "Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders",

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.",

author = "Jakob Seidlitz and Ajay Nadig and Siyuan Liu and Bethlehem, {Richard A.I.} and V{\'e}rtes, {Petra E.} and Morgan, {Sarah E.} and Franti{\v s}ek V{\'a}{\v s}a and Rafael Romero-Garcia and Lalonde, {Fran{\c c}ois M.} and Clasen, {Liv S.} and Blumenthal, {Jonathan D.} and Casey Paquola and Boris Bernhardt and Konrad Wagstyl and Damon Polioudakis and {de la Torre-Ubieta}, Luis and Geschwind, {Daniel H.} and Han, {Joan C.} and Lee, {Nancy R.} and Murphy, {Declan G.} and Bullmore, {Edward T.} and Armin Raznahan and Sarah Morgan",

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Seidlitz, J, Nadig, A, Liu, S, Bethlehem, RAI, Vértes, PE, Morgan, SE, Váša, F, Romero-Garcia, R, Lalonde, FM, Clasen, LS, Blumenthal, JD, Paquola, C, Bernhardt, B, Wagstyl, K, Polioudakis, D, de la Torre-Ubieta, L, Geschwind, DH, Han, JC, Lee, NR, Murphy, DG, Bullmore, ET, Raznahan, A & Morgan, S 2020, 'Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders', Nature Communications, vol. 11, no. 1, 3358. https://doi.org/10.1038/s41467-020-17051-5

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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

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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.

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SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

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Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

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