Our Stephen S. Rich, PhD, and collaborators have completed the largest and most diverse genetic study of type 1 diabetes ever undertaken, revealing new treatment targets and dramatically advancing our understanding of the genetic underpinnings of the disease.
Type 1 diabetes was once called juvenile diabetes, but it actually affects both children and adults. It type 1 diabetes, the immune system attacks the insulin-producing beta-cells in the pancreas, leaving the body unable to produce enough insulin. Treatment is insulin replacement, but there is no cure.
The sweeping new study identifies promising targets for new drugs to treat or prevent the disease. Some of those targets already have prospects in the pipeline: Drugs targeting 12 genes identified in the study have been tested or are being tested in clinical trials for autoimmune diseases. That could help accelerate their path to the clinic for use against type 1 diabetes, the researchers say.
Importantly, the new study significantly expands our understanding of the "genetic landscape" of the disease in people of African, Asian and other backgrounds, the scientists report in a new paper outlining their findings. Most prior research has focused primarily on diabetes risk in people of European ancestry.
“Increasing diversity in all aspects of research is ethically important but, in addition, diverse populations potentially provide unique genetic insights that can reduce the number of putatively causal variants on risk, as well as interactions with novel non-genetic risk factors,” said Rich, of our Department of Public Health Sciences and Center for Public Health Genomics. “For example, in African-ancestry populations, there is evidence in some genomic regions the type 1 diabetes risk variants have narrowed the list of causal variants, while in other regions, the risk variants are distinct from those in European-ancestry populations. These data are critical for implementing genetic risk scores for identifying those children at high genetic risk for future screening and entry into immune-intervention trials.”
In total, the scientists looked at data from 61,427 participants, twice as many as the previous largest study. From that, they were able to identify 78 chromosome regions that influence risk for type 1 diabetes. Of those, 36 were unknown.
In addition, the researchers identified specific, naturally occurring gene variations that influence risk and determined how those variations act on particular cell types.
“Based upon this work, we are now approaching knowledge of almost 90% of the genetic risk for type 1 diabetes, which is about one-half of the total risk for the disease,” Rich said. “This work moves us closer to the goal of precision medicine in type 1 diabetes, when we can use genetics to help identify those at risk for autoantibody screening and early detection, with genetic insights to therapies that would enhance the search for a cure.”