An international team of researchers, led by the University of Massachusetts Amherst and Helmholtz Munich, has identified hundreds of genes and proteins that are likely to play a causal role in Type 2 diabetes. The study, published in Nature Metabolism, highlights the importance of examining multiple tissues and diverse populations to understand the disease.
The research analyzed genetic data from over 2.5 million people worldwide. By comparing results across seven diabetes-relevant tissues and four global ancestry groups, the study found that relying solely on blood samples can miss significant aspects of Type 2 diabetes biology. Blood is often used for molecular studies due to its accessibility, but Type 2 diabetes involves several organs such as adipose tissue, liver, skeletal muscle, and pancreatic cells.
Researchers identified causal evidence for 676 genes across these tissues. Only a small portion—18%—of genes with a causal effect in primary diabetes tissues like the pancreas also showed signals in blood samples. Conversely, most gene effects detected in key tissues did not appear in blood.
"By revealing both shared and tissue-specific mechanisms, our findings move us closer to improving strategies for Type 2 diabetes prevention and treatments that may be more effective across global populations," said Chi "Josh" Zhao, a doctoral student at UMass Amherst and co-first author of the study.
The work draws on data from the Type 2 Diabetes Global Genomics Initiative—a consortium representing diverse populations—and builds on previous genome-wide association studies identifying thousands of DNA variants linked to diabetes risk. In this analysis, researchers looked at how these variants affect gene activity and protein levels among populations from Europe, Africa, the Americas, and East Asia. More than 20,000 genes and over 1,600 proteins were tested.
Results showed strong evidence that genetically predicted levels of 335 genes and 46 proteins influence Type 2 diabetes risk. Some associations were consistent across all ancestry groups; others became apparent only when including data from underrepresented populations.
The findings provide direction for future research into biological pathways involved in Type 2 diabetes with an aim toward developing more effective treatments.
