Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Briefing
  • Published:

Three patterns link brain organization to genes in health and disease

Gene expression in the human cortex is shown to exhibit a generalizable three-component architecture that reflects neuronal, metabolic, and immune programmes of healthy brain development. The three components have distinct associations with autism spectrum disorder and schizophrenia, revealing connections between previously unrelated results from studies of case–control neuroimaging, differential gene expression, and genetic risk.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Three components of gene expression reveal convergent links between healthy brain organization and neurodevelopmental disorders.


  1. Hawrylycz, M. J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012). The original paper presenting the AHBA, in which principal components of cortical gene expression were suggested to reflect brain organization.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Burt, J. B. et al. Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography. Nat. Neurosci. 21, 1251–1259 (2018). This paper characterizes the first component of cortical gene expression, C1, as reflecting a neuronal hierarchy defined by tract-tracing and indexed by structural neuroimaging.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sydnor, V. J. et al. Neurodevelopment of the association cortices: patterns, mechanisms, and implications for psychopathology. Neuron 109, 2820–2846 (2021). This review proposes that neurodevelopment involves a ‘sensorimotor–association axis’ defined by ten brain maps, of which one is the cortical gene expression component C1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Merikangas, A. K. et al. What genes are differentially expressed in individuals with schizophrenia? A systematic review. Mol. Psychiatry 27, 1373–1383 (2022). This review demonstrates the lack of consistency in genes linked to schizophrenia across differential expression studies, which are also inconsistent with GWAS.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Johnson, M. B. & Hyman, S. E. A critical perspective on the synaptic pruning hypothesis of schizophrenia pathogenesis. Biol. Psychiatry 92, 440–442 (2022). This commentary calls for an understanding of synaptic pruning in schizophrenia compared with healthy adolescent neurodevelopment.

    Article  PubMed  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Dear, R. et al. Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia. Nat. Neurosci. (2024).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Three patterns link brain organization to genes in health and disease. Nat Neurosci 27, 1044–1045 (2024).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing