Summary: A new study reveals that ancient viral DNA sequences, once thought to be “junk DNA,” are active in the human brain and contribute to the risk of psychiatric disorders like schizophrenia, bipolar disorder, and depression. This discovery sheds light on the complex genetic factors influencing mental health.
Key Facts:
- Ancient viral DNA sequences are expressed in the human brain.
- Some of these sequences are linked to increased risk for psychiatric disorders.
- Understanding these ancient viruses could revolutionize mental health research and treatment.
Source: King’s College London
New research led by King’s College London has found that thousands of DNA sequences originating from ancient viral infections are expressed in the brain, with some contributing to susceptibility for psychiatric disorders such as schizophrenia, bipolar disorder, and depression.
Published in Nature Communications, the study was part-funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the US National Institutes of Health (NIH).
About eight percent of our genome is comprised of sequences called Human Endogenous Retroviruses (HERVs), which are products of ancient viral infections that occurred hundreds of thousands of years ago.
Until recently, it was assumed that these ‘fossil viruses’ were simply junk DNA, with no important function in the body.
However, due to advances in genomics research, scientists have now discovered where in our DNA these fossil viruses are located, enabling us to better understand when they are expressed and what functions they may have.
This new study builds upon these advances and is the first to show that a set of specific HERVs expressed in the human brain contribute to psychiatric disorder susceptibility, marking a step forward in understanding the complex genetic components that contribute to these conditions.
Dr Timothy Powell, co-senior author on the study and Senior Lecturer at the Institute of Psychiatry, Psychology & 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”.
The study analysed data from large genetic studies involving tens of thousands of people, both with and without mental health conditions, as well as information from autopsy brain samples from 800 individuals, to explore how DNA variations linked to psychiatric disorders affect the expression of HERVs.
Although most genetic risk variants linked to psychiatric diagnoses impacted 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 signatures associated with psychiatric disorders, including two HERVs 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 and researcher at the Feinstein Institutes for Medical Research at Northwell Health, in the US, 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”.
About this mental health and genetics research news
Author: Franca Davenport
Source: King’s College London
Contact: Franca Davenport – King’s College London
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions” by Timothy Powell et al. Nature Communications
Abstract
Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions
Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role in aetiology remains unclear.
Here, we perform specialised transcriptome-wide association studies that consider HERV expression quantified to precise genomic locations, using RNA sequencing and genetic data from 792 post-mortem brain samples.
In Europeans, we identify 1238 HERVs with expression regulated in cis, of which 26 represent expression signals associated with psychiatric disorders, with ten being conditionally independent from neighbouring expression signals.
Of these, five are additionally significant in fine-mapping analyses and thus are considered high confidence risk HERVs.
These include two HERV expression signatures specific to schizophrenia risk, one shared between schizophrenia and bipolar disorder, and one specific to major depressive disorder.
No robust signatures are identified for autism spectrum conditions or attention deficit hyperactivity disorder in Europeans, or for any psychiatric trait in other ancestries, although this is likely a result of relatively limited statistical power.
Ultimately, our study highlights extensive HERV expression and regulation in the adult cortex, including in association with psychiatric disorder risk, therefore providing a rationale for exploring neurological HERV expression in complex neuropsychiatric traits.
