Six New Genes Associated With Type 2 Diabetes Discovered, Including One With Role In Prostate Cancer

The new findings bring the total number of genes or genomic regions implicated in diabetes to 16, said Laura Scott, assistant research scientist in the Department of Biostatistics. Researchers from the University of Michigan were one of three teams of scientists in Europe and North America that led the multi-group collaboration. The findings, which were published March 30 in the journal Nature Genetics, provide new insights into the mechanisms which are usually responsible for the control of glucose, or sugar, levels in the blood, and to the derangements that can result in type 2 diabetes, which impacts more than 170 million people worldwide.

One of the newly discovered genes, which goes by the name of JAZF1, contains a separate variant that has recently been shown to play a role in prostate cancer, and is the second gene that appears to play a role in both conditions. The first identified overlap between genes for prostate cancer and type 2 diabetes was with HNF1B, which is also involved in an early onset form of diabetes discovered at U-M in an unrelated study, called Maturity Onset Diabetes of the Young (MODY). In HNF1B, the same variant that is associated with increased risk of diabetes is associated with decreased risk of prostate cancer. In JAZF1, the diabetes and prostate cancer variants reside in different parts of the gene and there is no known relationship between them.

"Genetic studies of this kind are revealing new and unsuspected connections between diseases," says Dr Eleftheria Zeggini from the University of Oxford, first author on the paper. "This is now the second example of a gene which affects both type 2 diabetes and prostate cancer. We don't yet know what the connections are, but this has important implications for the future design of drugs for these conditions".

"Some of these genes for type 2 diabetes might be involved in diseases other than prostate cancer, in fact there is already a known overlap with heart disease in another genomic region" Scott said. "We have about 25,000 genes, and we've found a very small number by genome wide studies, so to have the same genomic regions come up in studies of different diseases is actually pretty interesting."

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body's inability to utilize insulin to move blood sugar into the cells for energy. Type 2 diabetes affects nearly 21 million in the United States and the incidence of the disease has skyrocketed in the last 30 years. Diabetes is a major cause of heart disease and stroke, as well as the most common cause of blindness, kidney failure and amputations in U.S. adults.

"The remarkable recent progress in identifying regions of the genome that increase risk to diabetes---from 3 to 16 in only a year---will help us unravel the complex basis diabetes and may suggest new and better tailored methods to prevent or treat this disease.," said U-M's Michael Boehnke, the lead scientist on the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group, one of the three lead groups in the study.

The researchers in this project set out to find differences in the genetic code that contribute to individual differences in susceptibility to disease. Previous efforts from these groups and others identified ten genes contributing to type 2 diabetes risk.