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Genetics of Kidneys in Diabetes (GoKinD) Study: A Genetics Collection Available for Identifying Genetic Susceptibility Factors for Diabetic Nephropathy in Type 1 Diabetes

Patricia W. Mueller^*, John J. Rogus, Patricia A. Cleary, Yuan Zhao, Adam M. Smiles, Michael W. Steffes, Jean Bucksa, Therese B. Gibson^||, Suzanne K. Cordovado^*, Andrzej S. Krolewski, Concepcion R. Nierras^¶ and James H. Warram

^* Centers for Disease Control and Prevention, Diabetes and Molecular Risk Assessment Laboratory, Atlanta, Georgia; Research Division, Joslin Diabetes Center, Boston, Massachusetts; George Washington University Biostatistics Center, Washington, DC; University of Minnesota, Minneapolis, Minnesota; ^|| Aspen Systems, Inc., Rockville, Maryland; and ^¶ Juvenile Diabetes Research Foundation, New York, New York

Address correspondence to: Dr. James H. Warram, Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. Phone: 617-732-2668; Fax: 617-732-2667; E-mail: james.warram{at}joslin.harvard.edu

The Genetics of Kidneys in Diabetes (GoKinD) study is an initiative that aims to identify genes that are involved in diabetic nephropathy. A large number of individuals with type 1 diabetes were screened to identify two subsets, one with clear-cut kidney disease and another with normal renal status despite long-term diabetes. Those who met additional entry criteria and consented to participate were enrolled. When possible, both parents also were enrolled to form family trios. As of November 2005, GoKinD included 3075 participants who comprise 671 case singletons, 623 control singletons, 272 case trios, and 323 control trios. Interested investigators may request the DNA collection and corresponding clinical data for GoKinD participants using the instructions and application form that are available at http://www.gokind.org/access. Participating scientists will have access to three data sets, each with distinct advantages. The set of 1294 singletons has adequate power to detect a wide range of genetic effects, even those of modest size. The set of case trios, which has adequate power to detect effects of moderate size, is not susceptible to false-positive results because of population substructure. The set of control trios is critical for excluding certain false-positive results that can occur in case trios and may be particularly useful for testing gene–environment interactions. Integration of the evidence from these three components into a single, unified analysis presents a challenge. This overview of the GoKinD study examines in detail the power of each study component and discusses analytic challenges that investigators will face in using this resource.

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