Ancient viral DNA in the human genome linked to major psychiatric disorders
Last reviewed: 14.06.2024
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New research led by King's College London has found that thousands of DNA sequences derived from ancient viral infections are expressed in the brain, some of which contribute to susceptibility to mental disorders such as schizophrenia, bipolar disorder and depression.
The work was published in the Nature Communications magazine.
About 8% of our genome consists of sequences called human endogenous retroviruses (HERVs), which are the products of ancient viral infections that occurred hundreds of thousands of years ago. Until recently, it was believed that these "viral fossils" were simply "junk" DNA with no important function in the body. However, thanks to advances in genomic research, scientists can now determine where these viral fossils are found in our DNA, allowing us to better understand when they are expressed and what functions they may serve.
This new study builds on these advances and shows for the first time that a set of specific HERVs expressed in the human brain contribute to susceptibility to psychiatric disorders, a step forward in understanding the complex genetic components that contribute to these conditions.
Dr Timothy Powell, co-author of the study and senior lecturer at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King's College London, said: "This study uses a new and robust approach to assess how genetic vulnerability to mental disorders influences the expression of ancient viral sequences present in the modern human genome. Our results indicate that these viral sequences likely play a more important role in the human brain than previously thought, with specific HERV expression profiles associated with increased susceptibility to certain psychiatric disorders."
The study analyzed data from large genetic studies involving tens of thousands of people, both with and without mental disorders, as well as information from brain samples taken at autopsies from 800 people, to examine how DNA variations are associated with mental disorders, affect the expression of HERVs.
Although most genetic risk variants associated with psychiatric diagnoses affected genes with well-known biological functions, the researchers found that some genetic risk variants preferentially affected the expression of HERVs. The researchers reported five robust HERV expression profiles associated with mental disorders, including two HERVs that are associated with risk for schizophrenia, one with risk for both bipolar disorder and schizophrenia, and one with risk for depression.
Dr Rodrigo Duarte, first author and IoPPN Fellow at King's College London, said: "We know that mental disorders have a significant genetic component, with many parts of the genome gradually contributing to susceptibility. In our study, we were able to examine the parts of the genome that correspond HERVs, which led to the identification of five sequences that are relevant to mental disorders. Although it is not yet clear how these HERVs influence brain cells to cause increased risk, our results suggest that regulating their expression is important for brain function. P>
Dr Douglas Nixon, study co-author and researcher at the Feinstein Institutes of Medical Research at Northwell Health, US, said: "Further research is needed to understand the precise function of most HERVs, including those identified in our study. We believe a better understanding These ancient viruses and known genes involved in mental disorders could revolutionize mental health research and lead to the development of new treatments or diagnoses for these conditions."