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  • Ancient Viral Sequences in Human Brain Linked to Psychiatric Disorders

    New research from King’s College London has discovered that thousands of DNA sequences originating from ancient viral infections are expressed in the brain, with some contributing to the susceptibility to psychiatric disorders such as schizophrenia, bipolar disorder, and depression.

    Study Background and Funding
    Published in Nature Communications, this study focuses on Human Endogenous Retroviruses (HERVs), sequences comprising about eight percent of our genome, remnants of ancient viral infections that occurred hundreds of thousands of years ago. Historically, these ‘fossil viruses’ were considered non-functional, but advances in genomics research have provided new insights into their locations and potential functions in human DNA.

    Genomics Advances Illuminate HERV Functionality
    This groundbreaking study builds upon recent genomic advancements, marking the first time a specific set of HERVs expressed in the human brain have been linked to psychiatric disorder susceptibility. Dr. Timothy Powell, co-senior author and Senior Lecturer at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, stated, “This study uses a novel and robust approach to assess how genetic susceptibility for psychiatric disorders imparts its effects on the expression of ancient viral sequences present in the modern human genome. Our results suggest that these viral sequences probably play a more important role in the human brain than originally thought, with specific HERV expression profiles being associated with an increased susceptibility for some psychiatric disorders.”

    Data Analysis and Findings
    The research team analyzed data from large genetic studies involving tens of thousands of individuals, both with and without mental health conditions. They also examined autopsy brain samples from 800 individuals to explore how DNA variations linked to psychiatric disorders affect HERV expression. Although most genetic risk variants impacted genes with known biological functions, the researchers identified five robust HERV expression signatures associated with psychiatric disorders. This includes two HERVs linked to schizophrenia risk, one linked to both bipolar disorder and schizophrenia, and one linked to depression risk.

    Dr. Rodrigo Duarte, first author and Research Fellow at the IoPPN, commented, “We know that psychiatric disorders have a substantial genetic component, with many parts of the genome incrementally contributing to susceptibility. In our study, we were able to investigate parts of the genome corresponding to HERVs, which led to the identification of five sequences that are relevant to psychiatric disorders. Whilst it is not clear yet how these HERVs affect brain cells to confer this increase in risk, our findings suggest that their expression regulation is important for brain function.”

    Future Research and Implications
    Dr. Douglas Nixon, co-senior author and researcher at the Feinstein Institutes for Medical Research at Northwell Health in the US, emphasized the need for further research, stating, “Further research is needed to understand the exact function of most HERVs, including those identified in our study. We think that a better understanding of these ancient viruses, and the known genes implicated in psychiatric disorders, have the potential to revolutionize mental health research and lead to novel ways to treat or diagnose these conditions.”

    Publication Details
    The study, titled Integrating Human Endogenous Retroviruses into Transcriptome-Wide Association Studies Highlights Novel Risk Factors for Major Psychiatric Conditions by Duarte, R.R.R., et al., is available in Nature Communications (DOI: 10.1038/s41467-024-48153-z).

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