Five HERV expression signatures linked to psychiatric disorders

Posted: 23 May 2024 | | No comments yet

This is the first study to demonstrate that a specific set of HERVs expressed in the human brain contribute to disorders like schizophrenia.

 Led by King’s College London, a new study has discovered that thousands of DNA sequences originating from ancient viral infections are expressed in the brain. Some of these sequences contribute to the susceptibility to psychiatric disorders like depression, schizophrenia, and bipolar disorder.

Sequences named Human Endogenous Retroviruses (HERVs) comprise around eight percent of the human genome. These have resulted from ancient viral infections that happened hundreds of millennia’s ago, and they were thought as, until recently, junk DNA, with no significant function in the body. Owing to advances in genomics, scientists have now found where in our DNA these fossil viruses are located, enabling an improved understanding of when they are expressed and what functions they may have.

This new research is the first to demonstrate 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 & Neuroscience (IoPPN), King’s College London, explained: “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.”

Analysing data from large genetic studies involving people both with and without mental health diseases, as well as information from autopsy brain samples from 800 individuals, the team investigated how DNA variations associated with psychiatric disorders alter the expression of HERVs.

Most genetic risk variants associated with psychiatric diagnoses impact genes with well-known biological functions. However, the scientists discovered that certain genetic risk variants preferentially affected the expression of HERVs. Five robust HERV expression signatures associated with psychiatric disorders were reported, including two HERVs that are linked to risk for schizophrenia, one linked to risk for both bipolar disorder and schizophrenia, and one linked to risk for depression.

Dr Rodrigo Duarte, first author and Research Fellow at the IoPPN, King’s College London, stated: “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, in the US, concluded: “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.”

This study was published in Nature Communications.