Large study sheds new light on the complex type 1 diabetes genetics landscape and potential drug targets
Conducting the largest and most ancestrally diverse study of type 1 diabetes genetics thus far, researchers have identified new regions of the genome associated with the disease and potential drug targets. In recent years, there has been tremendous research progress in understanding genetic contributors to type 1 diabetes, an autoimmune disease in which the insulin-producing cells in the pancreas are destroyed by the immune system. However, most studies have only included people of European ancestry. Less is known about genetic risk for type 1 diabetes in people with other ancestries, who are experiencing increasing rates of the disease. Additionally, little is known about how genetic variants associated with type 1 diabetes cause disease. This information has implications for understanding the disease process and developing future strategies to prevent or treat type 1 diabetes.
In new research, scientists analyzed genetic contributors to type 1 diabetes by studying over 61,000 participants (with and without the disease), including individuals from diverse ancestries. This approach led to the identification of 36 new gene regions associated with type 1 diabetes, some of which are also associated with other autoimmune diseases. Additionally, the scientists did “fine mapping” studies to pinpoint the specific disease-causing variants in genetic regions previously associated with type 1 diabetes, toward elucidating the role these variants may play in the disease process. In another set of experiments, they used their genetic association results with data about other autoimmune diseases to identify 12 genes that could potentially be drug targets for type 1 diabetes. Drugs targeting these genes (by affecting the proteins the genes encode) have been studied in clinical trials for other autoimmune diseases, suggesting they could be repurposed for type 1 diabetes. Some of the targets are already being studied in type 1 diabetes clinical trials of various therapies, but others could potentially be explored in future trials to prevent type 1 diabetes.
This large research study with a diverse population has provided important knowledge about the complex type 1 diabetes genetics landscape, revealing new genetic regions associated with the disease, shedding light on how some genetic variants may influence disease, and identifying potential drug targets. Understanding what genes play a role in type 1 diabetes, and what role they play, paves the way to identify new targets to prevent or treat this autoimmune disease.
Robertson CC, Inshaw JRJ, Onengut-Gumuscu S,…Rich SS. Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes. Nat Genet 53: 962-971, 2021.