Study identifies new gene variants linked with risk of T2D

Children's Hospital of Philadelphia researcher is co-leader of international study

The largest genetics study to date of type 2 diabetes (T2D) has identified new gene variants associated with risk for the common metabolic disease. An international scientific consortium, studying multiethnic populations, uncovered genes that may point to biological targets for developing more effective drugs for T2D.

Multiple genes and environmental factors interact with T2D, which affects nearly 300 million people worldwide. The majority of the gene variants remain undiscovered.

"Scientists have identified only about 10 percent of the genetic variants contributing to T2D, and most previous studies have been based on people of European ancestry," said senior co-author Brendan J. Keating, Ph.D., of the Center for Applied Genomics at The Children's Hospital of Philadelphia. This international study found that many gene variants associated with T2D overlap across multiple ethnic groups." The current study included subjects with African-American, Hispanic, Asian and European ancestry.

The study appears online today in the American Journal of Human Genetics. The study's other senior co-author was Richa Saxena, Ph.D., from Massachusetts General Hospital and Harvard Medical School.

The research consortium performed a meta-analysis of 39 existing studies of multiethnic populations, comprising over 17,000 cases of individuals with T2D, compared to 70,000 control subjects. This large-scale genetic screening used a customized gene analysis tool to examine 50,000 genetic variants across 2,100 genes known to be associated with cardiovascular and metabolic functions.

The researchers identified variants in four previously unknown genes associated with T2D, discovered six new independent genetic signals in known T2D genes, and verified 16 previously reported T2D-linked variants. A total of nearly 40 gene variants have now been found to raise or lower the risk of T2D. Keating says the current study's genome-wide screening approach in large multi-ethnic samples should be effective in discovering additional diabetes gene variants relevant to multiple ethnic populations.

Type 2 diabetes, previously called non-insulin dependent diabetes or adult-onset diabetes, accounts for 90 to 95 percent of all diabetes. It is a chronic metabolic disease in which the body produces insufficient insulin or becomes unable to properly process insulin it does produce. While the risk of T2D generally rises with age, the disorder has been significantly increasing among children and adolescents.

"As we continue to identify more genes associated with type 2 diabetes, we expect that further investigation of their specific biological functions will guide researchers toward new therapies for preventing and treating this disease," said Keating.