Three teams working together report that they identified at least three new genes and one new DNA region associated with increased risk of type 2 diabetes and confirmed the existence of another six.
First, the genomes of more than 2,300 Finnish people, part of the Finland-U.S. Investigation Of NIDDM Genetics (FUSION) and Finrisk 2002 studies, were scanned. About half of the participants had type 2 diabetes and the other half had normal blood glucose levels. To validate their findings, the researchers compared their results with data from genome scans of 3,000 Swedish and Finnish participants and 5,000 British participants. The Swedish and Finnish volunteers were from a collaboration of the Broad Institute of Harvard and MIT, Lund University, and Novartis. The British participants were from the Wellcome Trust Case Control Consortium.
After identifying promising leads through this approach, the three research teams say they jointly replicated their findings using smaller, more focused sets of genetic markers in additional groups totaling more than 22,000 people from Finland, Poland, Sweden, the U.K., and U.S. Totally, the genomes of over 32,000 people were tested for the study, according to the scientists.
The newly identified diabetes-associated variations lie in or near: IGF2BP2, which codes for insulin-like growth factor 2 mRNA binding protein 2; CDKAL1, which codes for CDK5 a regulatory subunit associated protein1-like1; and CDKN2A or CDKN2B, which produces proteins that inhibit the activity of cyclin-dependent protein kinases.
For each of these three genes, the Wellcome Trust group say they found that there are two common versions, one of which is associated with an increased risk of developing type 2 diabetes and the other with reduced risk. Each high-risk version increases the risk of getting the disease by 10% to 20%.
The investigators also found an association located in a region of chromosome 11 not known to contain any genes. They speculate that the variant sequences may regulate the activity of genes located elsewhere in the genome.
The genetic variants associated with diabetes that were confirmed are TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, and FTO, according to NHGRI.
The studies appear together in the April 26 advance online edition of Science. The U.S.-Finnish team was led by researchers from the University of Michigan's School of Public Health, the NHGRI, the University of Southern California, the University of North Carolina, the University of Helsinki, and the National Public Health Institute in Finland.