Genetic hyperlink discovered between diabetes and bone fracture threat


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A new method for studying gene function shows how high blood sugar and bone density are related in diabetes patients.

Scientists have discovered thousands of genetic variants – tiny changes in the genetic code – that are linked to an increased risk of various diseases. Learning what these variants do in the body is the key to translating genetic knowledge into new precision drugs. Now, researchers at the Broad Institute of MIT and at Harvard, Beth Israel Deaconess Medical Center, Harvard Medical School, and others have developed a number of techniques that researchers refer to as the Variant-to-Function (V2F) framework, and which they use can help efficiently Decipher the function of genetic variants – especially pleiotropic variants that affect multiple traits.

In a study published in Cell Metabolism, researchers used the framework to find a genetic link that may explain why patients with type 2 diabetes have increased bone mineral density while still being more prone to fractures. They identified a variant of chromosome 3 that increases the risk of both hyperglycemia or high blood sugar, and high bone density – two common symptoms in these patients. The team also demonstrated the mechanism of how the variant does this.

“The work provides a kind of framework that enables you to learn more about genetic risk sites that are pleiotropic in nature,” said Melina Claussnitzer, a member of the Broad Institute, director of the Biology of Aging Program at Beth Israel Deaconess Medical Center and at Harvard Medical School and senior study author.

She and her team developed the V2F toolkit in 2015 and are now showing for the first time that it can be used to identify the biological mechanism of a pleiotropic variant. Claussnitzer adds that researchers can use the toolkit to find biological links between symptoms of other diseases, which could provide clues for the development of new therapies.

In the study, the team identified the variant that contributes to a high risk of blood sugar and bone fractures by looking at data from genome-wide association studies that focused on diabetes and bone characteristics. They found that the variant occurs in a non-coding region of the ADCY5 gene that is involved in lipid metabolism. The variant reduces the expression of the gene, which leads to metabolic problems in fat cells and a type of bone cell called osteoblasts. This metabolic dysfunction in fat cells leads to high blood sugar and in bone cells to excessively high bone density, which can make bones more fragile.

Claussnitzer says therapy that reverses the effects of the variant could potentially treat symptoms of type 2 diabetes as well as high bone mineral density.

Claussnitzer’s group is now optimizing the methodology from variant to function in order to examine more variants and their interaction. “We are practically not looking at a single place right now, we’re enlarging it and taking a more global view,” she said.

In a long-term study, dozens of new genetic markers were found that are linked to lifelong bone growth

More information:
Nasa Sinnott-Armstrong et al. A regulatory variant in 3q21.1 confers an increased pleiotropic risk of hyperglycemia and altered bone mineral density, Cell Metabolism (2021). DOI: 10.1016 / j.cmet.2021.01.001 Provided by the Broad Institute of MIT and Harvard

Quote: Genetic association between diabetes and bone fracture risk (2021, February 4) found on February 6, 2021 from

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