NIH-Supported Research Outlines the Genetic Architecture of Type 2 Diabetes

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The influence of genetics on the risk for type 2 diabetes has been suggested by previous research, but new research from the National Institutes of Health (NIH) has now outlined in unprecedented detail the role of common genetic variants in the risk for this disease (Nature (2016 Jul 11. Epub ahead of print). It was previously thought that fewer and less common genetic variants play a role in type 2 diabetes (unlike type 1 diabetes, which is clearly based in genetic influences).

A team of international researchers supported by the NIH analyzed the DNA sequencing of more than 120,000 people with ancestral ties to Europe, South and East Asia, the Americas, and Africa. Study participants had their entire genome sequenced or only the part that codes directly for proteins (ie, the exome). Genetic changes between healthy participants and those with type 2 diabetes were compared, allowing researchers to determine the influence of the differences between rare and common DNA. Common differences in the genetic code rather than the rare codes were found to be associated with an increased risk for type 2 diabetes.

“Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies,” the researchers concluded.

Although most of the variants had been previously identified, more than a dozen genes were found to alter the structure or composition of the proteins they encod, suggesting that those genes are directly involved in type 2 diabetes.

“Our study has taken us to the most complete understanding yet of the genetic architecture of type 2 diabetes,” said Michael Boehnke, PhD, Director, Center for Statistical Genetics at the University of Michigan School of Public Health, Ann Arbor, and co-lead investigator of the study. “With this in-depth analysis we have obtained a more complete picture of the number and characteristics of the genetic variants that influence type 2 diabetes risk.”

According to the American Diabetes Association, nearly 10% of the US population has diabetes, with 1.4 million new cases diagnosed annually. There are a number of risk factors for type 2 diabetes, including family history and environmental causes. This study suggests that personalized treatments will need to be based on a patient’s broader genetic profile as well as on environmental factors.

“Our study tells us that genetic risk for type 2 diabetes reflects hundreds or even thousands of different genetic variants, most of them shared across populations,” said Jason Flannick, PhD, MD, Senior Group Leader, Broad Institute of Harvard and MIT, and co-lead investigator of the study. “This large range of genetic effects may challenge efforts to deliver personalized (or precision) medicine. However, to ensure that these challenges can be taken up by the wider research community, we have made the data from our study publicly accessible for researchers around the world in the hope that this will accelerate efforts to understand, prevent and treat this condition.”

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Last modified: February 14, 2019
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