Major Collaboration Uncovers Surprising New Genetic Clues to Diabetes

Analysis identifies potential new therapeutic targets; suggests possible ties to prostate cancer An international team that included scientists from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), last week reported it has identified six more genetic variants involved in type 2 diabetes, boosting to 16 the total number of genetic risk factors associated with increased risk of the disease. None of the genetic variants uncovered by the new study had previously been suspected of playing a role in type 2 diabetes. Intriguingly, the new variant most strongly associated with type 2 diabetes also was recently implicated in a very different condition: prostate cancer.

The unprecedented analysis, published in Nature Genetics, combined genetic data from more than 70,000 people. The work was carried out through the collaborative efforts of more than 90 researchers at more than 40 centers in Europe and North America.

"None of the genes we have found was previously on the radar screen of diabetes researchers," said one of the paper’s senior authors, Mark McCarthy, M.D., of the University of Oxford in England. "Each of these genes, therefore, provides new clues to the processes that go wrong when diabetes develops, and each provides an opportunity for the generation of new approaches for treating or preventing this condition."

When considered individually, the genetic variants discovered to date account for only small differences in the risk of developing type 2 diabetes. But researchers say when all of the variants are analyzed together, some significant differences in risk are likely to emerge. "By combining information from the large number of genes now implicated in diabetes risk, it may be possible to use genetic tools to identify people at unusually high or low risk of diabetes. However, until we know how to use this information to prompt beneficial changes in people’s treatment or lifestyle, widespread genetic testing would be premature," said another senior author, David Altshuler, M.D., Ph.D., of Massachusetts General Hospital in Boston.

"These new variants, along with other recent genetic findings, provide a window into disease causation that may be our best hope for the next generation of therapeutics. By pinpointing particular pathways involved in diabetes risk, these discoveries can empower new approaches to understanding environmental influences and to the development of new, more precisely targeted drugs," said NHGRI Director Francis S. Collins, M.D., Ph.D., who is a co-author of the study.

Researchers said more work is needed to understand the impact of their discovery that a genetic variant called JAZF1 appears to be involved in diabetes as well as prostate cancer. One of the study’s lead authors, Eleftheria Zeggini, Ph.D., of the University of Oxford, said, "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 may have important implications for the future design of drugs for both of these conditions."

For more information about genome-wide association studies, go to www.genome.gov/20019523.