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Uncovering Genetics Contributing to Diabetes Health Disparities

Researchers scanning the genome have uncovered genetic factors that may account for at least part of the elevated risk for type 2 diabetes in African American and South Asian populations. Detailed maps of common genetic variation derived from the Human Genome and HapMap projects have led to a renaissance in the ability to study the genetics of human disease. For example, geneticists using the genome wide association studies (GWAS) approach have found over 60 gene regions that affect risk for type 2 diabetes. However, while genetic factors are thought to contribute significantly to the higher burden of the disease in many non white populations, the early studies focused on people of European descent. This was because the genome maps originally designed for GWAS analysis had not adequately captured genetic variation common in non-white populations to permit these studies. To better understand how genes affect diabetes health disparities, researchers have redesigned these tools and begun using them to perform GWAS with samples that are specific to populations with the highest burden of type 2 diabetes.

In one study, researchers used GWAS to look for genetic differences between African Americans who either had or did not have type 2 diabetes. Genetic markers that were more common in one group than in the other were then confirmed using samples from a larger number of African American study participants. This approach led to the discovery of one novel genomic location that appears clearly to influence the risk for type 2 diabetes in African Americans, as well as four other genomic locations that may be involved, although the data are less certain.

In a separate study, researchers examined DNA samples from South Asians, a population which also has elevated risk for type 2 diabetes relative to people of European heritage. This approach led to the discovery of six genomic regions affecting type 2 diabetes risk in South Asian peoples. One of these regions includes GRB14, a gene encoding a protein that binds the insulin receptor and is thought to affect insulin sensitivity. Mice lacking GRB14 are lean, and more sensitive to insulin than normal mice. Another region includes HNF4A, a gene in which previously discovered mutations were found to reduce pancreatic insulin production and cause a rare disease called maturity onset diabetes of the young. While neither study reported discovering the precise genetic differences within the identified genomic regions that promote type 2 diabetes in African Americans or South Asians, or that provide Caucasians with relative protection from the disease, further studies looking in the 11 genomic regions identified by the 2 studies could begin to explain the cause of type 2 diabetes health disparities.


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