‘Core’ genes linked to type 1 diabetes revealed for the first time

Nine ‘core’ genes that are key to the development of type 1 diabetes have been identified, which could pave the way for new immunotherapies targeting the condition.

The research, which has been funded by Diabetes UK, has “broken new ground” in the understanding of the genes which are central to the development of type 1 diabetes.

The nine genes, which are all linked to the immune system, show for the first time, new immune pathways that have a crucial role in type 1 diabetes development.

The condition is caused by a mix of genetic and environmental factors, so knowing more about the genes linked to type 1 diabetes and how they control processes within the body, can shed further light on why some people develop the condition. This in turn presents opportunities for intervention.

Previous research has identified individual genes found to have a very small, cumulative effect on the risk of type 1 diabetes development and – in combination with environmental triggers – play a role in its development.

Dr Elizabeth Robertson, Director of Research at Diabetes UK, said: “Type 1 diabetes is a constant balancing act of blood sugar checks and insulin injections. We desperately need to find ways to prevent, delay and treat the condition, to spare hundreds of thousands of people the burden of managing their diabetes, day in, day out.

“This research has broken new ground in our understanding of genes that underpin type 1 diabetes, and how they contribute to the immune attack that causes the condition. The discovery that these ‘core’ immune system genes are central to the development of type 1 diabetes opens the door to a raft of new targets for immunotherapies that could prevent, delay or treat type 1 diabetes early on.

“With the first ever type 1 diabetes immunotherapy approved for use in the US last year, we are on the brink of a new era for type 1 diabetes therapies that could see it transformed from a lifelong condition to one that can be prevented, treated and ultimately cured.”

The study, which led by Professor Helen Colhoun and Professor Paul McKeigue at the University of Edinburgh, saw the development of a new way of analysing how different genes affect the risk of type 1 diabetes. The goal was to highlight which genes play a major role in the development of the condition and which only have a small impact.

Genetic data from nearly 5,000 people with type 1 diabetes and 7,500 people without the condition was analysed, along with blood samples.

The team examined how genes regulate the activity of other genes, allowing them to identify nine ‘core’ genes that have a significant effect on the risk of developing type 1 diabetes. All of these genes are linked to the immune system, with seven playing a vital role in the regulation of immune cells that attack the pancreas in people with type 1 diabetes.

Two of the ‘core’ genes are linked to the immune system’s first line of defence, which detects threats including viruses and bacteria, and the attack that is launched in response. This area of the immune system has not been linked to type 1 diabetes in the past.

The findings mean that immunotherapies could be developed and used to target these pathways to slow or prevent the development of type 1 diabetes. The very first immunotherapy – teplizumab – that can delay the onset of type 1 diabetes for up to three years was approved for use in the US last year.

The latest findings could help experts to develop an armoury of treatments in the face of the immune system’s many lines of attack.

Professor Paul McKeigue, from the University of Edinburgh, said: “At the beginning of the genome era in 2000, it was expected that the discovery of genes through which common variants cause disease, would rapidly lead to the development of new drugs.

“Until now researchers have studied the short-range effects of risk variants on nearby genes and found no obvious link to the risk of conditions or ways to treat them. Our study focused instead on the long-range effects of these risk variants on genes elsewhere on the genome. We have identified what appear to be ‘core’ genes for type 1 diabetes, some of which are potential therapeutic targets.”

Read the full study in American Journal of Human Genetics.

To find out more about Diabetes UK’s latest research projects visit diabetes.org.uk.

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