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Genetic studies reveal insights into ancestry-related differences in type 2 diabetes

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The onset and progression of type 2 diabetes is influenced by numerous biological processes, including the body’s response to insulin, the health of the insulin-producing pancreatic beta cells, and the function of metabolic pathways.

In a recent study published in natural medicine A team led by researchers at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard University analyzed individuals from diverse backgrounds and identified a wide range of organisms that may help explain ancestry-related differences in Type 2. We identified various gene clusters involved in the biological mechanisms. Clinical symptoms of diabetes.

Type 2 diabetes, which affects about 1 in 10 people in the United States, is an increase in blood sugar levels that can lead to serious health complications and is usually incurable. Why certain people develop this disease and why there is so much variation in clinical features among people with this disease is not fully understood at this time. ”

Miriam S. Udler, MD, senior author, director of the MGH Diabetes Genetics Clinic, and assistant professor at Harvard Medical School

Udler and colleagues evaluated the genetic findings of more than 1.4 million individuals across a variety of genetic ancestry backgrounds, including African/African American, mixed-race American, East Asian, European, South Asian, and multiple ancestry Did.

The analysis resulted in a final set of 650 genetic variants with independent associations with type 2 diabetes and a final list of 110 clinical traits associated with diabetes.

The scientists’ analysis validated diabetes-related gene clusters identified in previous studies. (A gene cluster is a group of two or more genetic regions suspected of sharing a generalized biological function).

The study identified a new gene cluster associated with lower cholesterol levels, abnormal bilirubin metabolism (produced when the body breaks down hemoglobin from aging red blood cells), and abnormal lipid handling in adipose and liver tissues. was also revealed.

Researchers identified 12 gene clusters associated with type 2 diabetes and their biological functions, and the clusters help explain some of the differences in type 2 diabetes between different populations. I discovered that.

For example, it is well established that individuals from various populations who identify as non-white are more likely to develop type 2 diabetes at certain BMIs.

Study data suggests that this difference is at least partially explained by two clusters of mutations the researchers identified that are related to how the body uses and stores fat. Asians who carry certain mutations in these clusters (most often people from the East) have a higher risk of type 2 diabetes at lower BMI levels than other people.

This finding could help clinicians calculate an individual’s target BMI level based on their genetic profile.

“Our study shows that the genetic basis of type 2 diabetes helps explain clinical differences between populations,” said co-first author and computational biologist at the MGH Center for Genomic Medicine. says Kirk Smith, Master of Arts. “Also, the genetic mechanisms of disease that we have identified offer the potential to guide the development of curative therapies,” said co-lead author Aaron J. Deutsch, M.D., Ph.D., an instructor in MGH’s Division of Endocrinology. added.

Other authors include Carolyn McGrail, Hyun-Kyung Kim, Sara Su, Alicia Huerta-Chagoya, Ravi Mandla, Philip H. Schroeder, Kenneth E. Westerman, Lukasz Szczerbinski, and Timothy D. Majarian, Varinderpal Kaur, Alice Williamson, Noah Theilen, Melina Kraussnitzer, Jose C. Flores, Alisa K. Manning, Josep M. Mercader, Kyle J. Galton.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Doris Duke Foundation, the American Diabetes Association, and the Novo Nordisk Foundation.


Reference magazines:

Smith, K. other. (2024). Multi-ancestral polygenic mechanisms of type 2 diabetes. natural medicine. doi.org/10.1038/s41591-024-02865-3.

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