Largest and most diverse genome-wide association study of type 2 diabetes reveals new genetic factors

By studying a diversity of participants, scientists find nearly 150 new locations in the genome linked to type 2 diabetes risk.

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An international collaboration of research teams has conducted the largest and most ancestrally diverse genome-wide association study for type 2 diabetes (T2D). By analyzing the DNA of 2.5 million participants, the researchers identified over 600 regions in the genome that are associated with increased risk for T2D, including 145 that had not been previously linked to the disorder. They recently reported their findings in Nature.

“Most studies lack sufficient diversity and are primarily based on data from European ancestry,” said Josep Mercader, a group leader in the Diabetes Research Group at the Broad Institute of MIT and Harvard, a computational biologist at Massachusetts General Hospital, and one of the paper’s 11 senior authors. “This study reduces that gap by increasing the ancestral diversity.”

The meta-analysis was a massive collaborative effort primarily led by the University of Manchester, the Helmholtz Institute of Translational Genomics, the National Human Genome Research Institute, the University of Michigan, the University of Pennsylvania, and UCLA. Other Broad researchers who contributed to the study include co-first author Ravi Mandla and Alicia Huerta. The Broad Institute, in partnership with the Mass General Brigham Biobank and the SIGMA Consortium, contributed a significant portion of the study’s genetic data from people of Latin American and African American ancestry. 

Genetic variants strongly influence a person’s likelihood of developing T2D and a better understanding of the genetics of T2D could lead to better ways of preventing and treating T2D. Despite T2D’s disproportionate prevalence in people from under-represented ancestry groups, most diabetes genetics studies focus on patients of European ancestry.  

“It’s important to perform studies not only in large populations, but also in diverse populations. Some of these findings would not have been discovered if we studied only a single population,” said Mercader.

Mercader and his co-authors say that their results could help advance research on the genetics of T2D and other complex diseases, and hope that their work encourages more studies on larger and more diverse populations. 

“There is still a long way to go before genetic studies are ancestrally equitable,” said Mercader. “But this is a great resource for better understanding pathophysiology of type 2 diabetes across ancestries, identifying new drug targets, and developing prediction and preventative strategies.”
 

Funding

Support for this study was provided by the Japan Agency for Medical Research and Development, the National Human Genome Research Institute, the American Heart Association, the American Diabetes Association, the National Institute of Diabetes and Digestive and Kidney Diseases, Versus Arthritis, the UK National Institute for Health and Care Research, and more sources.

Paper cited

Suzuki K, Hatzikotoulas K, Southam L, Taylor H, Yin X, Lorenz K, Mandla R, et al. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature Metabolism. Online February 19, 2024. DOI: 10.1038/s41586-024-07019-6