Digging Deeper into the Role of Genetics in Type 1 Diabetes
Type 1 diabetes is a complex disease. While researchers know what it does to the body, they are still unclear on exactly why this happen and what triggers this response. Advances in genetic testing have led scientists to identify more than 50 genome regions that may be associated with type 1 diabetes. It is clear that there is not a single gene responsible for this disease, but rather many that all play a part.
In addition, researchers have determined that genetics are not the sole determinant of whether an individual develops type 1 diabetes (T1D); environmental factors are also responsible. This makes it even more challenging to pinpoint what causes T1D and who is most at risk. However, the more scientists understand about both the genetic and environmental causes, the closer they can get to potentially preventing the disease. This is critical because there has been a nearly 30% increase in Americans diagnosed with T1D since 2017 according to the CDC’s National Diabetes Statistics Report.
Type 1 diabetes can run in families, and having a first-degree family member with the disease can put individuals at greater risk. Researchers have identified two genes in particular that are of interest – HLA-DRB1 and HLA-DQB1 – which are both located on the human leukocyte antigen (HLA) complex on chromosome 6p21. Individuals who have both of these genes account for about 40% of T1D cases, but just because someone has both genes does not necessarily mean they will develop T1D. Likewise, there are many people who do not have these two genes who go on to be diagnosed with the disease. In twin studies, if one twin had T1D, only about 50% of co-twins developed it as well, demonstrating that it is not solely genetic (nor solely environmental).
Another interesting finding was that children were at greater risk of islet autoimmunity if their father or a sibling had T1D, as opposed to if their mother had it. Furthermore, the study showed that “children with a second-degree relative with type 2 diabetes showed significantly delayed progression from islet autoimmunity to clinical type 1 diabetes vs. children without such relatives.” This data was collected through The Environmental Determinants of Diabetes in the Young (TEDDY) study, which includes children from the United States, Finland, Germany, and Sweden.
These types of studies have made researchers re-evaluate the potential risk factors for the disease and how to effectively predict susceptibility. They have been trying to fine-tune an approved genetic risk score assessment to include more recent data regarding islet autoantibodies, age, and metabolic factors used to track disease progression. Calculating a genetic risk score that encompasses many different pieces of information and parameters may help researchers improve predictive modeling. In turn, this may help with prevention efforts.
There are a lot of different factors that may contribute to the development of T1D, and all of this has helped researchers generate more focused studies to support prevention. The Diabetes Research Connection (DRC) has raised funds for numerous early-career scientists pursuing research in this area, but more funding and research are needed to keep moving forward. As new cases of type 1 diabetes continue to rise, there has been a greater push for prediction and prevention efforts. Learn more about current DRC projects and how to help by visiting https://diabetesresearchconnection.org.