Three components of human brain gene expression reflect normative developmental programmes with specific links to neurodevelopmental disorders Article Swipe
Richard Dear
,
Konrad Wagstyl
,
Jakob Seidlitz
,
Ross D. Markello
,
Aurina Arnatkevičiūtė
,
Kevin M. Anderson
,
Richard A.I. Bethlehem
,
Armin Raznahan
,
Edward T. Bullmore
,
Petra E. Vértes
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.10.05.510582
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.10.05.510582
Human brain organisation emerges from the coordinated transcription of thousands of genes, and the first principal component (C1) of spatial whole genome expression was shown to reflect cortical hierarchy. Here, optimised processing of the Allen Human Brain Atlas revealed two new components of brain transcription, C2 and C3, which were distinctively enriched for neuronal, metabolic and immune processes, cell-types and cytoarchitecture, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas, and BrainSpan), we found that C1-C3 represent generalisable transcriptional programmes that are coordinated within cells, and differentially phased during foetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, gene expression, and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional programme for adolescent brain development, which can lead to atypical supragranular brain connectivity in people at high genetic risk for schizophrenia.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.10.05.510582
- https://www.biorxiv.org/content/biorxiv/early/2023/07/18/2022.10.05.510582.full.pdf
- OA Status
- green
- Cited By
- 4
- References
- 118
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4302425992
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- OpenAlex ID
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https://openalex.org/W4302425992Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.10.05.510582Digital Object Identifier
- Title
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Three components of human brain gene expression reflect normative developmental programmes with specific links to neurodevelopmental disordersWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-10-06Full publication date if available
- Authors
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Richard Dear, Konrad Wagstyl, Jakob Seidlitz, Ross D. Markello, Aurina Arnatkevičiūtė, Kevin M. Anderson, Richard A.I. Bethlehem, Armin Raznahan, Edward T. Bullmore, Petra E. VértesList of authors in order
- Landing page
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https://doi.org/10.1101/2022.10.05.510582Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/07/18/2022.10.05.510582.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2023/07/18/2022.10.05.510582.full.pdfDirect OA link when available
- Concepts
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Autism, Human brain, Neuroscience, Biology, Brain atlas, Neuroimaging, Cytoarchitecture, Schizophrenia (object-oriented programming), Gene, Psychology, Genetics, Developmental psychology, PsychiatryTop concepts (fields/topics) attached by OpenAlex
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4Total citation count in OpenAlex
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2024: 1, 2023: 1, 2022: 2Per-year citation counts (last 5 years)
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118Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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