Institute of Genetics and Cancer

Core genes for type 1 diabetes revealed

Researchers have identified nine core genes that play a key role in increasing the risk of developing type 1 diabetes.

A girl has a glucose monitor fitted by a healthcare professional

Only four of the genes identified have previously been linked to type 1 diabetes in humans.

The research team, including Professor Helen Colhoun and Professor Caroline Hayward of the Institute of Genetics and Cancer and Professor Paul McKeigue of the Usher Institute, say the findings could lead to the development of new therapies to prevent and treat the condition, which affects an estimated 400,000 people in the UK.

A new theory of the genetics of diseases divides genes into two main categories: core genes that have a direct impact on the development of disease, and regulator genes which have an indirect impact through their interaction with core genes. This is the first time core genes have been identified for type 1 diabetes.

Researchers used a new approach which explored the effect of common variants – changes to the DNA sequence – on genes throughout the genome. Previous studies exploring the link between common variants and type 1 diabetes have focused on the impact of any changes in genetic code on genes located nearby. These are known as “cis-” effects. The research team investigated the impact of common variants on the activity of genes located further away. These long-range influences of variants are known as “trans-” effects.

By adding up the long-range effects of several common variants, the research team found that their impact was focused on a small number of core genes. The method could also be applied to detect core genes in other conditions where common variants are known to cause disease.

Almost all of the genes identified by the study are involved in the immune system, which in type 1 diabetes mistakenly attacks the cells responsible for producing insulin.

The findings reveal promising targets for new drugs to prevent or reverse the autoimmune damage to the cells that produce insulin. The research team studied almost 5,000 people diagnosed with type 1 diabetes and 7,500 healthy individuals in Scotland, from the Scottish Diabetes Research Network Type 1 Bioresource and the Generation Scotland study.

The study, supported by Diabetes UK, is published in the American Journal of Human Genetics.

 

At the beginning of the genome era in 2000, it was envisaged that the discovery of genes through which common variants cause disease would rapidly lead to development of new drugs. Until now this has been disappointing. Studying the short-range effects of these variants on nearby genes has rarely identified promising drug targets. We have focused instead on the long-range “trans-” effects of these risk variants on genes elsewhere on the genome. This identifies what appear to be “core” genes for type 1 diabetes, some of which are possible drug targets.

Professor Paul McKeigueUsher Institute

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