The discovery provides a more complete picture of the genetics and biological processes underlying type 2 diabetes, with some clear patterns emerging.
The international team, led by researchers from the University of Oxford, the Broad Institute of Harvard and MIT, and the University of Michigan, used a new DNA chip to probe deeper into the genetic variations that commonly occur in DNA, and which may have some connection to type 2 diabetes.
U-M researchers on the team from the U-M School of Public Health Department of Biostatistics include Michael Boehnke, Richard G Cornell Distinguished University Professor of Biostatistics; Goncalo Abecasis, Felix Moore Collegiate Professor of Biostatistics; Hyun Min Kang, assistant professor of biostatistics; Laura Scott, associate research scientist and adjunct associate professor of biostatistics; Tanya M. Teslovich, research fellow; Anne U. Jackson, research area specialist lead; and Heather M. Stringham, research area specialist lead.
Their findings are published in the journal Nature Genetics.
“The paper, in identifying 10 new gene regions as playing a role in type 2 diabetes risk, adds to our understanding of the basic biology of type 2 diabetes, Boehnke said. “For example, our findings suggest that hundreds of common genetic variants contribute to type 2 diabetes risk.
“These new gene regions provide additional targets for possible drug development and more specific tailoring for diabetes therapies,” he said.
The American Diabetes Association estimates there are 25.8 million individuals with diabetes in the United States, or 8.3 percent of the population. Of these, some 7 million are undiagnosed. Another 79 million people are considered pre-diabetic, which means they have higher than normal blood glucose levels and are at increased risk of developing type 2 diabetes.
Left untreated, diabetes can cause many different health problems including heart disease, stroke, nerve damage, and blindness. Even a mildly raised glucose level can have damaging effects in the long-term.
The researchers analyzed DNA from nearly 35,000 people with type 2 diabetes and approximately 115,000 people without, identifying 10 new gene regions where DNA changes reliably could be linked to risk of the disease. Two of these showed different effects in men and women, one linked to greater diabetes risk in men and the other in women.
U-M’s Hyun Min Kang was the key designer of the metabochip used to analyze the genetic variations.
The metabochip is a genotyping array—or collection of microscopic DNA spots attached to a solid surface—used to map genomic regions by researchers who are studying metabolic or cardiovascular traits in DNA. The chip allows researchers to look at up to 200,000 DNA sequence variations, using a highly efficient and sensitive technology more powerful than previous techniques, at a significant cost savings.
“Development of the metabochip was a collaborative effort across multiple research groups studying metabolic traits, and individual research groups made a significant effort to genotype and analyze the data, and the outcomes are now coming out, including the type 2 diabetes results and results for glucose and insulin traits” Kang said.
With more than 60 genes and gene regions now linked to type 2 diabetes, the researchers were able to find patterns in the types of genes implicated in the disease. Although each individual gene variant has only a small influence on a person’s overall risk of diabetes, the types of genes involved are giving new insight into the biology behind diabetes.
“We see genes involved in controlling the process of cell growth, division and aging, particularly those that are active in the pancreas where insulin is produced. We see genes involved in pathways through which the body’s fat cells can influence biological processes elsewhere in the body. And we see a set of transcription factor genes – genes that help control what other genes are active,” said Professor Mark McCarthy of the Wellcome Trust Centre for Human Genetics at the University of Oxford.
While gene association studies have been successful in finding DNA regions that can reliably be linked to type 2 diabetes, it can be hard to tie down which gene and what exact DNA change is responsible.
The researchers’ next step is to get complete information about genetic changes driving type 2 diabetes by sequencing people’s DNA in full.
“We want to understand exactly which genes and which variants within those genes cause someone to be more or less susceptible to type 2 diabetes,” Teslovich said. “In parallel, we are performing sequencing in additional individuals to identify new loci and rare variants. Finally, it’s important to study these genes in the laboratory, in cell culture and in model organisms to understand their biology.”
Adapted with permission from a University of Oxford release
- Contact Laurel Thomas Gnagey