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Brain-based gene expression of putative risk genes for anorexia nervosa

Molecular Psychiatry volume 28, pages 2612–2619 (2023)Cite this article

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Abstract

The etiology of anorexia nervosa (AN) remains elusive. Recent genome-wide association studies identified the first genes liked to AN which reached genome-wide significance, although our understanding of how these genes confer risk remains preliminary. Here, we leverage the Allen Human Brain Atlas to characterize the spatially distributed gene expression patterns of genes linked to AN in the non-disordered human brain, developing whole-brain maps of AN gene expression. We found that genes associated with AN are most expressed in the brain, relative to all other body tissue types, and demonstrate gene-specific expression patterns which extend to cerebellar, temporal and basal ganglia structures in particular. fMRI meta-analyses reveal that AN gene expression maps correspond with functional brain activity involved in processing and anticipating appetitive and aversive cues. Findings offer novel insights around putative mechanisms through which genes associated with AN may confer risk.

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Fig. 1: Differential stability of protein coding genes.
Fig. 2: The pathway of gene expression for anorexia nervosa risk genes in the human brain.
Fig. 3: Cognitive state correlates of the five differentially stable genes associated with AN.
Fig. 4: Mental state correlates of the five differentially stable genes associated with AN.

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Authors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, University of Southern California, Los Angeles, CA, USA

    Stuart B. Murray

  2. Norwegian Centre for Mental Disorders Research (NORMENT), Division for Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway

    Jaroslav Rokicki, Alina M. Sartorius, Adriano Winterton, Ole A. Andreassen, Lars T. Westlye & Daniel S. Quintana

  3. Centre of Research and Education in Forensic Psychiatry, Oslo University Hospital, Oslo, Norway

    Jaroslav Rokicki

  4. Department of Psychology, University of Oslo, Oslo, Norway

    Alina M. Sartorius, Lars T. Westlye & Daniel S. Quintana

  5. Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway

    Adriano Winterton

  6. KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway

    Ole A. Andreassen, Lars T. Westlye & Daniel S. Quintana

  7. Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA

    Jason M. Nagata

  8. NevSom, Department of Rare Disorders and Disabilities, Oslo University Hospital, Oslo, Norway

    Daniel S. Quintana

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Contributions

SBM conceptualized the manuscript, interpreted statistical analyses, and wrote the initial draft. DSQ conceptualized the manuscript, performed statistical analyses, and interpreted statistical analyses. JR performed statistical analyses. AMS performed statistical analyses. All authors edited the final version of the manuscript.

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Correspondence to Daniel S. Quintana.

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41380_2023_2110_MOESM1_ESM.docx

Supplementary Table 1: Regional patterns of gene expression for genes linked to anorexia nervosa in the non-disordered human brain.

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Murray, S.B., Rokicki, J., Sartorius, A.M. et al. Brain-based gene expression of putative risk genes for anorexia nervosa. Mol Psychiatry 28, 2612–2619 (2023). https://doi.org/10.1038/s41380-023-02110-2

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