Researchers at the University of California San Diego School of Medicine have identified a predictive causal role for specific cell types in Type 1 diabetes by mapping its genetic underpinnings.
The mechanisms of Type 1 diabetes are poorly understood. Because it has a strong genetic component, numerous genome-wide association studies (GWAS) have been conducted. Researchers compare whole genomes of people with the same condition, searching for differences in the genetic code that may be associated with it.
In Type 1 diabetes, identified at-risk variants have primarily been found in the non-coding regions of the genome. The researchers integrated GWAS data with epigenomic maps of cell types in peripheral blood and the pancreas. Epigenomic mapping details how and when genes are turned on and off in cells, determining the production of proteins vital to specific cellular functions.
The study analysed 520,580 genome samples to identify 69 novel association signals. They then mapped 448,142 cis-regulatory elements (non-coding DNA sequences in or near a gene) in pancreas and peripheral blood cell types.
“By combining these two methodologies, we were able to identify cell type-specific functions of disease variants and discover a predictive causal role for pancreatic exocrine cells in type 1 diabetes, which we were able to validate experimentally,” said senior author Kyle Gaulton, PhD.
Co-author Maike Sander, MD, said the findings represent a significant leap in understanding the causes of type 1 diabetes.
The findings are published in the May 2021 issue of Nature.