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Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders

Author

Listed:
  • Jakob Seidlitz

    (National Institute of Mental Health
    University of Cambridge)

  • 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
    Queen Mary University of London
    The Alan Turing Institute)

  • 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
    McGill University)

  • Damon Polioudakis

    (Semel Institute, David Geffen School of Medicine, UCLA)

  • Luis Torre-Ubieta

    (Semel Institute, David Geffen School of Medicine, UCLA
    Semel Institute, David Geffen School of Medicine, UCLA)

  • Daniel H. Geschwind

    (Semel Institute, David Geffen School of Medicine, UCLA
    David Geffen School of Medicine, UCLA)

  • Joan C. Han

    (University of Tennessee Health Science Center and Le Bonheur Children’s Foundation Research Institute
    National Institute of Mental Health, NIH
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH)

  • Nancy R. Lee

    (Drexel University)

  • Declan G. Murphy

    (King’s College London)

  • Edward T. Bullmore

    (University of Cambridge
    Cambridgeshire and Peterborough NHS Foundation Trust)

  • Armin Raznahan

    (National Institute of Mental Health)

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.

Suggested Citation

  • 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. Blume, 2020. "Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17051-5
    DOI: 10.1038/s41467-020-17051-5
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    Cited by:

    1. Stuart Oldham & Gareth Ball, 2023. "A phylogenetically-conserved axis of thalamocortical connectivity in the human brain," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Justine Y. Hansen & Golia Shafiei & Jacob W. Vogel & Kelly Smart & Carrie E. Bearden & Martine Hoogman & Barbara Franke & Daan Rooij & Jan Buitelaar & Carrie R. McDonald & Sanjay M. Sisodiya & Lianne , 2022. "Local molecular and global connectomic contributions to cross-disorder cortical abnormalities," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. G. Ball & S. Oldham & V. Kyriakopoulou & L. Z. J. Williams & V. Karolis & A. Price & J. Hutter & M. L. Seal & A. Alexander-Bloch & J. V. Hajnal & A. D. Edwards & E. C. Robinson & J. Seidlitz, 2024. "Molecular signatures of cortical expansion in the human foetal brain," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Golia Shafiei & Ben D. Fulcher & Bradley Voytek & Theodore D. Satterthwaite & Sylvain Baillet & Bratislav Misic, 2023. "Neurophysiological signatures of cortical micro-architecture," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Aleksandr Talishinsky & Jonathan Downar & Petra E. Vértes & Jakob Seidlitz & Katharine Dunlop & Charles J. Lynch & Heather Whalley & Andrew McIntosh & Fidel Vila-Rodriguez & Zafiris J. Daskalakis & Da, 2022. "Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    6. Vincent Bazinet & Justine Y. Hansen & Reinder Vos de Wael & Boris C. Bernhardt & Martijn P. Heuvel & Bratislav Misic, 2023. "Assortative mixing in micro-architecturally annotated brain connectomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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