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IUPUI research discovers gene variants associated with diabetes


INDIANAPOLIS — Using Indiana University’s supercomputing capabilities, researchers have discovered rare and low-frequency gene variants associated with diabetes, a finding that adds to the understanding of the disease’s genetic causes, said Jennifer Wessel, an assistant professor of genomic epidemiology in the IU Richard M. Fairbanks School of Public Health and IU School of Medicine at Indiana University-Purdue University Indianapolis.

Wessel is first author of “Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility,” which was recently published in the journal Nature Communications.

“For people like me, who are focused on prevention, the finding is exciting because I can use this information, along with all the other variants that have been found and will be found in the future, to help predict which one of us is more likely to develop diabetes,” Wessel said. “As we improve our understanding of the biology of the disease, we will be better able to figure out how to treat the disease.”

The process used to discover the new findings was innovative. Combining data from 23 epidemiology studies from around the world, involving 60,564 non-diabetic individuals, researchers for the first time used the HumanExome BeadChip, a specially designed genetic variation chip, to search for rare and low-frequency gene variants across the human genome, Wessel said. Rare variants occur less than 1 percent of the time, while low-frequency variants occur between 1 and 5 percent of the time.

Previously, genome-wide association studies had been used to identify common variants, or variants that occur more than 5 percent of the time, associated with common diseases and traits. The cause of diabetes is about half genetics and half lifestyle choices.

Indiana University supercomputing capabilities were used to analyze the massive amount of data, which included single-variant and gene-based analyses of the non-diabetic individuals and 16,491 individuals with type 2 diabetes and 81,877 controls.  

“The idea was to go after the low-frequency and rare variants and see if that helps explain part of explaining the genetic variation of diseases like diabetes that we are interested in,” Wessel said.

“We found a low-frequency variant in GLP1R, which was found to lower glucose levels and risk for diabetes through lower early insulin secretion,” Wessel said.

Researchers had never found any variants in this gene associated with diabetes or glucose levels, and it is the first time a low-frequency variant has been found that is associated with diabetes and glucose levels, she said. According to Wessel, IU’s supercomputer made it possible to analyze the massive amount of data that is needed for current genetic discovery research. 

The research findings increase understanding of the pathways of the disease, which may eventually lead to the development of new and better drugs for treatment of diabetes. According to the Centers for Disease Control and Prevention, 29.1 million Americans have diabetes, which is one out of every 11. An additional 86 million Americans, or more than one in three, have prediabetes, which can progress to diabetes without weight loss and moderate physical activity.

The burden of this disease is significant. The total medical cost and lost work and wages for Americans with diagnosed diabetes is $245 billion, and the risk of death for adults with diabetes is an astonishing 50 percent higher than for adults without diabetes. In 2012, the last year for which data is available, 1.7 million adults were newly diagnosed with the disease.