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The relation between cortical gene expression and the neural correlates of risky behavior

Nature Mental Health (2024)Cite this article

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Abstract

Risky behavior is a heritable trait that can have negative mental health consequences. It has been associated with variability in cortical structure and function, but the relation between cortex, gene expression and risky behavior remains unclear. Here we investigated associations of structural and functional cortical measures with risky behavior in UK Biobank data (Nā€‰=ā€‰19,205) and examined relationships of the identified cortical patterns with regional gene expression. We found that expression of 49 genes that were previously associated with risky behavior (out of 152 tested) was linked to these cortical patterns. We also observed associations between the identified cortical patterns and gene expression related to psychiatric disorders and specific cortical cell types. Through whole-genome analysis, we selected all genes with expression linked to the identified cortical patterns and identified their associated biological pathways. These findings contribute to a deeper understanding of the neural mechanisms underlying the translation of genetic predispositions into risky behavior.

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Fig. 1: Overview of the study design.
Fig. 2: The associations between brain measures and risky behavior.
Fig. 3: Transcriptional signatures of genes significantly associated with risky behavior.
Fig. 4: Transcriptional signatures of dysregulated genes for psychiatric disorders.
Fig. 5: Transcriptional signatures of cell-specific genes.
Fig. 6: Whole-genome transcriptional signatures.

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Data availability

This research used data from the UKBB resource at https://biobank.ndph.ox.ac.uk/showcase/label.cgi?id=100. Access to UKBB data requires the submission and approval of a research project by the UKBB committee. Human gene expression data that support the findings of this study are available via the AHBA at http://human.brain-map.org/static/download. The GWAS summary statistics for risky behaviors can be downloaded via the SSGAC website at https://www.thessgac.org/. To access the GWAS summary statistics, an account on the SSGAC website is required. The dysregulated genes for psychiatric disorders are derived from the study by Gandal et al.45 (the data are deposited in the supplementary file named ā€˜aad6469_gandal_sm_data-table-s1.xlsxā€™). The cell-specific genes can be obtained from the study by Seidlitz et al.46 (Supplementary Data 5). The GO Biological Processes database are available via Zenodo at https://zenodo.org/records/4460714 (ref. 81).

Code availability

Python code on Jupyter notebook used for statistical analyses is available via GitHub at https://github.com/deeppsych/Shu_risky_behavior.

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Acknowledgments

This research has been conducted using the UKBB Resource under application number 30091. We thank the Allen Institute for Brain Science, SSGAC, University of California, Los Angeles and National Institute of Mental Health for sharing human gene expression data, GWAS summary statistics of risky behavior, the dysregulated genes for psychiatric disorders and cell-specific genes, respectively. This work was supported by China Scholarship Council (201904910604) and Yunnan Province (202305AH340006) to S.L. and an Amsterdam Neuroscience grant (PI: K.J.H.V.). A.A. and K.J.H.V. are supported by the Foundation Volksbond Rotterdam. G.v.W. has received research funding by Philips for an unrelated project.

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  1. These authors jointly supervised this work: Abdel Abdellaoui, Guido A. van Wingen, Karin J.H. Verweij.

Authors and Affiliations

  1. Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    Shu Liu,Ā Abdel Abdellaoui,Ā Guido A. van WingenĀ &Ā Karin J. H. Verweij

  2. Amsterdam Neuroscience, Amsterdam, The Netherlands

    Shu Liu,Ā Abdel Abdellaoui,Ā Guido A. van WingenĀ &Ā Karin J. H. Verweij

  3. Key Laboratory of Genetic Evolution and Animal Models, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China

    Shu Liu

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Contributions

S.L., A.A., G.v.W. and K.J.H.V. conceived and designed the study. S.L. analyzed the data, wrote the paper and revised the paper according to the reviewersā€™ comments. A.A., K.J.H.V. and G.v.W. provided subtantial feedback on the data analysis and the revision of the paper. A.A., K.J.H.V. and G.v.W. jointly supervised the work.

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Correspondence to Shu Liu or Karin J. H. Verweij.

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Supplementary Methods, Figs. 1ā€“6 and Table 14.

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Supplementary Tables 1ā€“13.

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Liu, S., Abdellaoui, A., van Wingen, G.A. et al. The relation between cortical gene expression and the neural correlates of risky behavior. Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00311-4

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