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CARDIOVASCULAR DISEASE

The regulatory network architecture of cardiometabolic diseases

Nature Genetics volume 54, pages 2–3 (2022)Cite this article

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Complex disease definitions often represent descriptive umbrella terms of symptoms rather than mechanistic entities. A new study shows how network-based approaches can help identify the mechanisms that link genes, cells, tissues and organs in cardiovascular diseases.

The work is based on the Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) study4, a large resource of transcriptomic data for cardiovascular diseases available to date, containing samples of various tissues and organs from more than 500 patients. This dataset allowed the authors to identify more than 200 gene modules with highly coordinated expression patterns. Machine-learning techniques were then used to extract potential regulatory interactions and key drivers. Taken together, the regulatory interactions comprise more than 40,000 independent expression-regulatory single-nucleotide polymorphisms (eSNPs), the collective contribution of which to heritability of coronary artery diseases was found to be up to 60%.

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Fig. 1: A mechanistic understanding of complex diseases requires a detailed mapping of the underlying perturbations across biological networks.

FrankRamspott / DigitalVision Vectors / Getty (proteome graphic); sumkinn / iStock / Getty Images Plus/Getty (transcriptome graphic)

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Authors and Affiliations

  1. Department of Pharmacology and Personalised Medicine, Faculty of Health and Medical Science, Maastricht University, Maastricht, The Netherlands

    Harald H. H. W. Schmidt

  2. Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Vienna, Austria

    Jörg Menche

  3. Faculty of Mathematics, University of Vienna, Vienna, Austria

    Jörg Menche

  4. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

    Jörg Menche

Authors
  1. Harald H. H. W. Schmidt
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  2. Jörg Menche
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Correspondence to Harald H. H. W. Schmidt or Jörg Menche.

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The authors declare no competing interests.

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Schmidt, H.H.H.W., Menche, J. The regulatory network architecture of cardiometabolic diseases. Nat Genet 54, 2–3 (2022). https://doi.org/10.1038/s41588-021-00994-w

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