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Ancient viral DNA linked to major psychiatric disorders, study suggests

It had previously been thought that these fossil viruses had no important function and were simply junk DNA.

Thousands of DNA sequences originating from ancient infections are found in the brain
Thousands of DNA sequences originating from ancient infections are found in the brain (David Davies/PA)

Ancient viral DNA still present in the human genome may be linked to major psychiatric disorders, research suggests.

Thousands of DNA sequences originating from ancient infections are found in the brain, with some contributing to susceptibility for conditions like schizophrenia, bipolar disorder, and depression, the study led by King’s College London found.

About 8% of the genome (the complete set of DNA) is made up of sequences called Human Endogenous Retroviruses (HERVs) – products of ancient viral infections that occurred hundreds of thousands of years ago.

It had been thought that these fossil viruses had no important function, and were simply junk DNA.

However, scientists have discovered where in our DNA these fossil viruses are located, helping them to understand what functions they may have.

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The study is the first to show that a set of specific HERVs expressed in the human brain contribute to psychiatric disorder susceptibility.

Dr Timothy Powell, co-senior author on the study and Senior Lecturer at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, said: “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”.

Researchers looked at data from large studies involving tens of thousands of people, both with and without mental health conditions, as well as information from autopsy brain samples from 800 people.

They found that some genes preferentially affected the expression of HERVs.

The researchers reported five robust HERV expression signatures associated with psychiatric disorders, including two that are associated with risk for schizophrenia, one associated with risk for both bipolar disorder and schizophrenia, and one associated with risk for depression.

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 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.”

Dr Douglas Nixon, co-senior author on the study and researcher at the Feinstein Institutes for Medical Research at Northwell Health, USA, said: “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 revolutionise mental health research and lead to novel ways to treat or diagnose these conditions”.

Published in Nature Communications, the study was part-funded by the National Institute for Health and Care Research (NIHR) and the US National Institutes of Health (NIH).