ANN ARBOR—An international team co-led by scientists from the University of Michigan have discovered 12 more regions on the genome with DNA variants that are associated with increased risk of type 2 diabetes, bringing the number to 38.

A variant is a place on a string of DNA where one of the “letters,” or nucleotides, differs between people. At most places along the DNA, any two people will have the same letter. The variable places in the DNA are important because some variants can increase predisposition to disease and other conditions, or offer drug targets.

Researchers also wanted to know if people who hadn’t yet developed type 2 diabetes but did have the diabetes variant showed elevated blood glucose levels, a main predictor of diabetes, said study co-leader Laura Scott, associate research scientist at the U-M School of Public Health.

“What our study suggests is that many of these variants are associated with changes in glucose levels long before people get diabetes,” said study co-leader Michael Boehnke, professor of biostatistics at U-M’s School of Public Health.

One surprising finding was that the regions with diabetes variants also seemed to be associated with nonrelated diseases. Researchers looked at a database containing a list of all the genome wide association (GWA) studies to date. They examined regions where there was a type 2 diabetes association to see if there was an increased association for other diseases and traits that have been studied thus far.

“We saw surprising overlap or predisposition of not just related but also apparently unrelated traits,” said Boehnke, who suggested that there could be master regulators in the genome that play a role in many different aspects of physiology and health.

The next step is to take the research beyond GWA, which looks at a few million places on the genome, into genome sequencing. Genome sequencing will allow researchers to assay most of the 3 billion base pairs in the human genome and find less common variants that might be associated with disease. Currently, a three-study international team co-led by the Michigan group is sequencing 2,650 individuals with and without diabetes, in what is one of the largest sequencing projects underway in the world. Scott and Boehnke hope to have information about the variants present in individuals with and without diabetes within the next year-and-a-half.

The paper, “Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis,” appeared online June 27 in Nature Genetics.

The University of Michigan School of Public Health has been working to promote health and prevent disease since 1941, and is consistently ranked among the top five public health schools in the nation. Whether making new discoveries in the lab or researching and educating in the field, SPH faculty, students and alumni are deployed around the globe to promote and protect our health.

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