14th June 2023:
Only four of the nine genes identified have previously been linked to type 1 diabetes in humans, and all nine are themselves linked to the immune system. Seven of these genes play a crucial role in controlling the immune cells responsible for attacking the pancreas in type 1 diabetes. Two of the genes are linked to part of the immune system’s first line of defence. This is responsible for detecting threats, like bacteria or viruses, and launching an immediate attack. These newly discovered immune processes hold great potential to be new targets for immunotherapies to prevent, delay or treat type 1 diabetes.
Researchers developed a new method of analysing the effect of common variants (changes to DNA sequence) on genes throughout the genome, and subsequently how different genes impact your risk of developing type 1 diabetes, by dividing genes into two main categories. Core genes that have a direct impact on the development of disease, and regulator genes that have an indirect impact through their interaction with core genes. This is the first time core genes have been identified for type 1 diabetes.
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.
The research team studied genetic data from 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 respectively, as well as analysing blood samples.