Genetic Sequencing Unlocks Potential Targets for Type 2 Diabetes Treatment

A worldwide investigation into the genetic underpinnings of type 2 diabetes (T2D) reveals that a combination of genetic variants, all working together, account for most of the genetic risk of the disease. The findings were published Monday in Nature.

DNA sequencing in 120,000 people, a project that involved more than 300 researchers, examined traits of people from every corner of the globe. Led by the University of Michigan, the University of Oxford, and the Broad Institute, the team included National Institutes of Health (NIH) Director Francis Collins, MD, PhD, who also heads the Molecular Genetics section at the National Human Genome Institute.

Researchers examined the entire genome for some patients, while another part of the study looked at the work of proteins, known as the exome. The project compared genetic changes in healthy people versus those with T2D. Collins described the effort in a blog post Tuesday as "unprecedented in its investigative scale and scope," saying that it "pulled together the largest-ever inventory of DNA sequence changes involved in T2D, and compared their distribution in people around the world."

"This 'Big Data' strategy has already yielded important new insights into the biology underlying the disease, some of which may yield novel approaches to diabetes treatment and prevention," Collins writes.

According to NIH, researchers wanted to settle the question of whether the genetic roots of T2D are caused by single, rare variants that occur in multiple people, or whether common genetic traits, each adding a small element of risk, work in concert to cause disease. It turns out that T2D arises from the genetic concoction.

“Variants associated with type 2 diabetes after sequencing were overwhelmingly common, and most fell within regions previously identified by genome-wide association studies,” the abstract said. “Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.”

While the study revealed several potential new targets for treatment, it also revealed the challenge of personalizing T2D treatment. An individual approach would need to account for individual genetic and environmental factors.

T2D incidence is rising in the United States and worldwide, with an estimated 10% of the global population diagnosed or at risk of developing the disease. A study from the American Diabetes Association put the 2012 economic impact of diabetes, most of which is from T2D, at $245 billion, from both healthcare costs and lost productivity. Diabetes accounts for $1 of every $3 spent by Medicare.

Reference

Fuchsberger C, Flannick J, Teslovich TM, et al. The genetic architecture of type 2 diabetes [published online July 11, 2016]. Nature. doi: 10.1038/nature18642.