University of Edinburgh team identifies key genetic risk factor after studying more than 1m people’s DNA
An extensive new study of the DNA of more than 1m people has identified the gene APOE as significant contributor to a person’s risk of developing delirium – a medical condition in which a person suffers sudden mental confusion.
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APOE is already well known to have a role in Alzheimer’s disease. The researchers found that even after adjusting for the presence of dementia, APOE’s effect on the risk of developing delirium remained significant. That strongly suggests that APOE contributes to delirium susceptibility independently, in people who are not living with dementia.
This is important because delirium affects about a quarter of all older adults in hospital. Delirium is also linked with higher risks of developing dementia and of death, and with longer hospital stays. Yet, at present, there are currently no specific treatments for the condition. It is hoped that by better understanding the genetics involved, we can develop targeted treatments and new ways to prevent the progression from delirium to dementia.
You can read the full paper, ‘Dissecting the genetic and proteomic risk factors for delirium’, in the journal Nature Aging.
The study is the largest and most diverse genetic analysis of delirium carried out to date. It drew on data from the UK, USA and Finland, provided by UK Biobank, FinnGen, All of Us Research Programme and the Michigan Genomics Initiative.
The team also examined blood samples from the UK Biobank taken from 32,000 individuals who developed delirium, collected up to 16 years before any such diagnosis. From these samples, the team identified several blood-based proteins that can be used to predict delirium risk years in advance, and markers of brain injury and inflammation. Some of these indicators have never previously been linked to delirium.
What’s more, the study suggests some potential leads for developing new treatments. The protein PON3 was shown to have a link with protection against delirium. This protein is thought to be involved in the processing of statins, which are medicines already in common use to lower cholesterol. That may mean we can repurpose existing medicines to effectively treat delirium – though of course more research is needed.
Researchers were based at the University of Edinburgh’s Usher and Roslin Institutes and School of Mathematics. The study was funded by the Vivensa Foundation and the Legal & General Group.
Vasilis Raptis, main author of the study, says: ‘The study provides the strongest evidence to date that delirium has a genetic component. Our next step is to understand how DNA modifications and changes in gene expression in brain cells can lead to delirium.’
Albert Tenesa, Professor of Quantitative Genetics at the University of Edinburgh, adds: ‘The findings shed new light on the biological foundations of delirium, suggesting that brain vulnerability, and systemic and nervous system inflammation may all play important roles. This opens new avenues for investigation not just of delirium itself, but also the poorly understood and very important link between delirium and future risk of dementia.’
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