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New Genetic Clues for Type 2 Diabetes Identified

In a new, large-scale gene-association study, an international team of scientists identified 38 new genetic regions that are associated with glucose and insulin levels in the blood.  Many of these regions also have an impact on the risk of type 2 diabetes. Laura J. Rasmussen-Torvik, PhD, Northwestern University Feinberg School of Medicine assistant professor of preventive medicine, contributed to the study, which was published in Nature Genetics.

“This study builds on previous GWAS (genome-wide association study) analyses that have looked for novel gene variations associated with blood insulin or blood glucose,” said Rasmussen-Torvik. “We included more individuals than previous studies and focused on gene variations thought most likely to be associated with diabetes and diabetes-related traits.”

The study brings the total number of genetic regions associated with glucose and insulin levels to 53, more than half of which are associated with type 2 diabetes.

Diabetes is a condition in which too much glucose, a type of sugar, exists in the blood. Type 2 diabetes is the most common form of diabetes, affecting some 90 percent of all people with diabetes. It is sometimes described as a "lifestyle disease" strongly associated with high blood pressure, high cholesterol, and obesity.

The researchers used a more powerful technology than previously employed to follow-up on genome-wide association results. The technology, Metabochip, was designed as a cost-effective way to find and map genomic regions for a range of cardiovascular and metabolic characteristics on a large scale. Previous approaches were not cost effective and tested only 30 to 40 DNA sequence variations, but Metabochip allowed researchers to investigate up to 200,000 DNA sequence variations for many different traits at one time. The team hoped to find new variants influencing blood glucose and insulin traits and to identify pathways involved in the regulation of insulin and glucose levels.

“GWAS meta-analyses require a tremendous amount of work from hundreds of coauthors because they involve analysis from many studies,” said Rasmussen-Torvik, whose role was to help with the analysis of genetic data from one such study, the Atherosclerosis Risk in Communities (ARIC) Study.

The team found additional, less significant genetic regions that may be associated with blood glucose and insulin levels, but currently don't have available data to definitively establish them as genome-wide significant. This supports previous evidence that a long tail of many other genetic regions adds up to smaller genetic effects, but may increase the risk of such diseases as diabetes. Collectively, these less significant associations may represent important blood glucose and insulin level associations.

While the Nature Genetics study focused on diabetes, Rasmussen-Torvik plans to expand the findings to other diseases.

“I’d like to examine the association of some of the gene variations highlighted in this study with atherosclerosis using a technique called Mendelian Randomization to determine if having elevated blood glucose actually directly causes an increase in atherosclerosis,” she said.

Rasmussen-Torvik’s work on this project was partly supported by the Atherosclerosis Risk in Communities study. ARIC is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and US NIH contract HHSN268200625226C.

For a full list of funding associated with this project, see the article acknowledgements.

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