GWAS Identifies Cell Type-Specific Functions of Type 1 Diabetes Variants

By mapping its genetic underpinnings, researchers at University of California San Diego School of Medicine have identified a predictive causal role for specific cell types in type 1 diabetes. Their findings were published in Nature.

Senior author Kyle Gaulton and colleagues integrated GWAS data with epigenomic maps of cell types in peripheral blood and the pancreas.  Specifically, researchers performed one of the largest to date GWAS of type 1 diabetes, analyzing 520,580 genome samples to identify 69 novel association signals. They then mapped 448,142 cis-regulatory elements 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 Gaulton.

Co-author Maike Sander, said the findings represent a major leap in understanding the causes of type 1 diabetes. "The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis," he concluded.