June 29, 2010 An international team co-led by scientists from the University of Michigan have discovered 12 more regions on the genome with DNA variants that are associated with increased risk of type 2 diabetes, bringing the number to 38.
A variant is a place on a string of DNA where one of the "letters," or nucleotides, differs between people. At most places along the DNA, any two people will have the same letter. The variable places in the DNA are important because some variants can increase predisposition to disease and other conditions, or offer drug targets.
Researchers also wanted to know if people who hadn't yet developed type 2 diabetes but did have the diabetes variant showed elevated blood glucose levels, a main predictor of diabetes, said study co-leader Laura Scott, associate research scientist at the U-M School of Public Health.
"What our study suggests is that many of these variants are associated with changes in glucose levels long before people get diabetes," said study co-leader Michael Boehnke, professor of biostatistics at U-M's School of Public Health.
One surprising finding was that the regions with diabetes variants also seemed to be associated with nonrelated diseases. Researchers looked at a database containing a list of all the genome wide association (GWA) studies to date. They examined regions where there was a type 2 diabetes association to see if there was an increased association for other diseases and traits that have been studied thus far.
"We saw surprising overlap or predisposition of not just related but also apparently unrelated traits," said Boehnke, who suggested that there could be master regulators in the genome that play a role in many different aspects of physiology and health.
The next step is to take the research beyond GWA, which looks at a few million places on the genome, into genome sequencing. Genome sequencing will allow researchers to assay most of the 3 billion base pairs in the human genome and find less common variants that might be associated with disease. Currently, a three-study international team co-led by the Michigan group is sequencing 2,650 individuals with and without diabetes, in what is one of the largest sequencing projects underway in the world. Scott and Boehnke hope to have information about the variants present in individuals with and without diabetes within the next year-and-a-half.
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- Benjamin F Voight, Laura J Scott, Valgerdur Steinthorsdottir, Andrew P Morris, Christian Dina, Ryan P Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S Aulchenko, Gudmar Thorleifsson, Laura J McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J Willer, Soumya Raychaudhuri, Steve A McCarroll, Claudia Langenberg, Oliver M Hofmann, Josée Dupuis, Lu Qi, Ayellet V Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J Bennett, Roza Blagieva, Eric Boerwinkle, Lori L Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noisël P Burtt, Guillaume Charpentier, Peter S Chines, Marilyn Cornelis, David J Couper, Gabe Crawford, Alex S F Doney, Katherine S Elliott, Amanda L Elliott, Michael R Erdos, Caroline S Fox, Christopher S Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Norman Klopp, Augustine Kong, Peter Kraft, Johanna Kuusisto, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A Morken, Narisu Narisu, Peter Nilsson, Katharine R Owen, Felicity Payne, John R B Perry, Ann-Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N William Rayner, Neil R Robertson, Ghislain Rocheleau, Michael Roden, Michael J Sampson, Richa Saxena, Beverley M Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M Stringham, Qi Sun, Amy J Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M van Dam, Timon W van Haeften, Thijs van Herpt, Jana V van Vliet-Ostaptchouk, G Bragi Walters, Michael N Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N Bergman, Stephane Cauchi, Francis S Collins, Anna L Gloyn, Ulf Gyllensten, Torben Hansen, Winston A Hide, Graham A Hitman, Albert Hofman, David J Hunter, Kristian Hveem, Markku Laakso, Karen L Mohlke, Andrew D Morris, Colin N A Palmer, Peter P Pramstaller, Igor Rudan, Eric Sijbrands, Lincoln D Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Nicholas J Wareham, Richard M Watanabe, Gonçalo R Abecasis, Bernhard O Boehm, Harry Campbell, Mark J Daly, Andrew T Hattersley, Frank B Hu, James B Meigs, James S Pankow, Oluf Pedersen, H-Erich Wichmann, Inês Barroso, Jose C Florez, Timothy M Frayling, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F Wilson, Thomas Illig, Philippe Froguel, Cornelia M van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I McCarthy. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genetics, 2010; DOI: 10.1038/ng.609
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