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Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia.
Dear, Richard; Wagstyl, Konrad; Seidlitz, Jakob; Markello, Ross D; Arnatkeviciute, Aurina; Anderson, Kevin M; Bethlehem, Richard A I; Raznahan, Armin; Bullmore, Edward T; Vértes, Petra E.
Afiliação
  • Dear R; Department of Psychiatry, University of Cambridge, Cambridge, UK. rajd2@cam.ac.uk.
  • Wagstyl K; Wellcome Centre for Human Neuroimaging, London, UK.
  • Seidlitz J; Lifespan Brain Institute, Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, PA, USA.
  • Markello RD; Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Arnatkeviciute A; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
  • Anderson KM; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
  • Bethlehem RAI; Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia.
  • Raznahan A; Department of Psychiatry, University of Cambridge, Cambridge, UK.
  • Vértes PE; Section on Developmental Neurogenomics, National Institute of Mental Health, Bethesda, MD, USA.
Nat Neurosci ; 27(6): 1075-1086, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38649755
ABSTRACT
Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1-C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esquizofrenia / Córtex Cerebral / Transcriptoma Limite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esquizofrenia / Córtex Cerebral / Transcriptoma Limite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article