Common Variants in Maturity-Onset Diabetes of the Young Genes Contribute to Risk of Type 2 Diabetes in Finns

Common Variants in Maturity-Onset Diabetes of the Young Genes Contribute to Risk of Type 2 Diabetes in Finns Lori L. Bonnycastle 1 , Cristen J. Willer 2 , Karen N. Conneely 2 , Anne U. Jackson 2 , Cecily P. Burrill 1 , Richard M. Watanabe 3 , Peter S. Chines 1 , Narisu Narisu 1 , Laura J. Scott 2 , Sareena T. Enloe 1 , Amy J. Swift 1 , William L. Duren 2 , Heather M. Stringham 2 , Michael R. Erdos 1 , Nancy L. Riebow 1 , Thomas A. Buchanan 4 , Timo T. Valle 5 , Jaakko Tuomilehto 5 6 7 , Richard N. Bergman 8 , Karen L. Mohlke 9 , Michael Boehnke 2 and Francis S. Collins 1 1 Genome Technology Branch, National Genome Research Institute, Bethesda, Maryland 2 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan 3 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 4 Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California 5 Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland 6 Department of Public Health, University of Helsinki, Helsinki, Finland 7 South Ostrobothnia Central Hospital, Seinäjoki, Finland 8 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 9 Department of Genetics, University of North Carolina, Chapel Hill, North Carolina Address correspondence and reprint requests to Francis S. Collins, MD, PhD, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-2152. E-mail: francisc{at}mail.nih.gov Abstract Prior reports have suggested that variants in the genes for maturity-onset diabetes of the young (MODY) may confer susceptibility to type 2 diabetes, but results have been conflicting and coverage of the MODY genes has been incomplete. To complement our previous studies of HNF4A , we examined the other five known MODY genes for association with type 2 diabetes in Finnish individuals. For each of the five genes, we selected 1 ) nonredundant single nucleotide polymorphisms (SNPs) ( r 2 < 0.8 with other SNPs) from the HapMap database or another linkage disequilibrium map, 2 ) SNPs with previously reported type 2 diabetes association, and 3 ) nonsynonymous coding SNPs. We tested 128 SNPs for association with type 2 diabetes in 786 index cases from type 2 diabetic families a