Remnants of ancient viruses in human DNA are linked to schizophrenia and depression

New research from King's College London has found that ancient viral DNA sequences known as human endogenous retroviruses (HERVs) are expressed in the brain and contribute to susceptibility to mental disorders. The study found that certain HERVs are linked to an increased risk of schizophrenia, bipolar disorder and depression. The researchers analyzed extensive genetic data and autopsy brain samples to uncover these links. The findings suggest that understanding the role of these viral sequences in brain function could revolutionize mental health research and lead to new treatment and diagnostic methods. Source:

Recent research has shown that DNA Remnants of ancient viruses in our genome are associated with an increased susceptibility to psychiatric disorders such as schizophrenia and depression, underscoring the significant, previously underestimated influence of these viral sequences on brain health.

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 illnesses such as schizophrenia, bipolar disorder and depression.

Published in Nature communicationThe study was partly funded by the Maudsley Biomedical Research Centre of the National Institute for Health and Care Research (NIHR) and the USA. National Institute of Health (NIH).

About eight percent of our genome is made up of sequences called human endogenous retroviruses (HERVs), products of ancient viral infections that occurred hundreds of thousands of years ago. Until recently, these “fossil viruses” were thought to be just DNA junk and had no important function in the body. However, thanks to advances in genomics, scientists have now discovered where in our DNA these fossil viruses are located. This allows us to better understand when they are expressed and what functions they may have.

New insights into psychiatric disorders

The new study builds on these advances by showing for the first time that a number of specific HERVs expressed in the human brain contribute to susceptibility to mental disorders, thus representing an advance in understanding the complex genetic components that contribute to these disorders.

Dr Timothy Powell, co-senior author of the study and lecturer at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, said: “This study uses a novel and robust approach to investigate how genetic susceptibility to psychiatric disorders affects the expression of ancient viral sequences present in the modern human genome. Our findings suggest that these viral sequences are likely to play a more important role in the human brain than previously thought, with certain HERV expression profiles associated with increased susceptibility to some psychiatric disorders.”

The study analyzed data from large genetic studies involving tens of thousands of people with and without mental illness, as well as information from autopsy brain samples from 800 people, to investigate how DNA variations associated with psychiatric disorders affect the expression of HERVs.

Although most genetic risk variants associated with psychiatric diagnoses affected genes with known biological functions, the researchers found that some genetic risk variants preferentially affected the expression of HERVs. The researchers reported five robust HERV expression signatures associated with psychiatric disorders, including two HERVs associated with risk for schizophrenia, one associated with risk for both bipolar disorder and schizophrenia, and one associated with risk for depression.

Impacts and future directions

Dr Rodrigo Duarte, first author and research fellow at the IoPPN, King's College London, said: “We know that psychiatric disorders have a substantial genetic component, with many parts of the genome contributing incrementally to susceptibility. In our study, we were able to examine parts of the genome corresponding to HERVs, leading to the identification of five sequences relevant to psychiatric disorders. Although it is not yet clear how these HERVs affect brain cells to cause this increased risk, our results suggest that their expression regulation is important for brain function.”

Dr Douglas Nixon, co-senior author of the study and researcher at the Feinstein Institutes for Medical Research at Northwell Health in the US, said: “Further research is needed to understand the precise function of most HERVs, including those identified in our study. We believe that a better understanding of these ancient viruses and the known genes associated with psychiatric disorders has the potential to revolutionise mental health research and lead to new treatments or diagnostics for these conditions.”

Reference: “Integration of human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for important psychiatric disorders” by Rodrigo RR Duarte, Oliver Pain, Matthew L. Bendall, Miguel de Mulder Rougvie, Jez L. Marston, Sashika Selvackadunco, Claire Troakes, Szi Kay Leung, Rosemary A. Bamford, Jonathan Mill, Paul F. O'Reilly, Deepak P. Srivastava, Douglas F. Nixon, and Timothy R. Powell, May 22, 2024, Nature communication.
DOI: 10.1038/s41467-024-48153-z

The study was funded by the National Institutes of Health.