01/29/2026 09:19
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Numerous genetic studies have pinpointed many risk variants for type 2 diabetes (T2D), but identifying which genes and proteins actually drive the disease has remained elusive. Now, an international team led by researchers at Helmholtz Munich has harnessed worldwide genetic data to uncover genes and proteins linked to T2D, systematically comparing results across multiple tissues and four global ancestry groups. Their findings, published today in the journal Nature Metabolism, demonstrate that many crucial signals would have been missed if analyses were limited to blood samples alone.
Beyond the Blood: Why Tissue Matters
For decades, blood has been the go-to for molecular studies, largely for practical reasons. But type 2 diabetes isn’t confined to the bloodstream; it’s a complex disease unfolding across a network of organs and cell types – including fatty tissue, the liver, muscles, and the insulin-producing cells of the pancreas. “Our analysis underscores just how incomplete it is to attempt to explain disease mechanisms using blood tests in isolation,” says Dr. Ozvan Bocher from the French Université de Bretagne Occidentale and the Institute for Translational Genomics at Helmholtz Munich, the study’s first author. “We identified causal evidence for 676 genes in seven diabetes-relevant tissues – and simultaneously found that the majority of these effects aren’t detectable in blood.”
The researchers quantified this finding: only 18% of genes with a causal effect in a key T2D tissue, like the pancreas, also showed a corresponding signal in blood. Conversely, a striking 85% of gene effects identified in T2D tissues were absent in blood samples.
“Our analyses clearly demonstrate that tissue context is critical for unraveling the mechanisms behind type 2 diabetes,” says study leader Prof. Eleftheria Zeggini, Director of the Institute for Translational Genomics at Helmholtz Munich and Professor of Translational Genomics at the Technical University of Munich (TUM).
Global Data Strengthens Findings
The study leveraged data from the Type 2 Diabetes Global Genomics Initiative (T2DGGI), an international consortium pooling genetic data from numerous studies worldwide to identify DNA variants associated with T2D risk through genome-wide association studies (GWAS). The T2DGGI analysis included data from over 2.5 million individuals, with more than 700,000 people of non-European descent.
“The study impressively showcases the power and relevance of international collaboration and comprehensive genomic data in uncovering the molecular mechanisms of complex metabolic diseases like type 2 diabetes,” says Prof. Martin Hrabě De Angelis, scientific director and spokesman for the management (acting) at Helmholtz Munich.
Uncovering Genetic Clues with cis-QTLs
The international team investigated how genetic variations in blood influence gene activity and protein levels – and whether these changes could illuminate the genetic causes of type 2 diabetes. They focused on cis-quantitative trait loci (cis-QTLs), genetic variants near a gene that measurably alter its activity or associated protein levels. The team analyzed 20,307 genes and 1,630 proteins across four ancestry groups: European, African, American, and East Asian.
“This provided strong evidence that the genetically predicted levels of 335 genes and 46 proteins could influence T2D risk,” says Ozvan Bocher. “Some of these findings are particularly promising because their effects have been replicated in independent datasets from other studies within the same ancestry groups.” While most effects were consistent across ancestry groups, certain candidates only emerged when underrepresented populations were included.
Big Data Illuminates the Path Forward
“Our results were only possible thanks to the availability of detailed molecular profiles of tissues relevant to type 2 diabetes,” says Zeggini. She adds, “It’s now clear that if we want to truly understand the mechanisms of type 2 diabetes and reliably translate findings into clinical practice, we must consider both tissue biology and genetic diversity.”
Original publication:
Bocher et al., 2026: Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues. Nature Metabolism. DOI: 10.1038/s42255-025-01444-1
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Journalists, Scientists and scholars
Biology, Medicine
transregional, national
Research results, Scientific Publications
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