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Mapping Genes for NIDDM: Design of the Finland—United States Investigation of NIDDM Genetics (FUSION) Study

  1. Timo Valle, MD,
  2. Jaakko Tuomilehto, MD, PHD,
  3. Richard N Bergman, PHD,
  4. Soumitra Ghosh, MD, PHD,
  5. Elizabeth R Hauser, PHD,
  6. Johan Eriksson, MD, PHD,
  7. Stella J Nylund, PHD,
  8. Kimmo Kohtamäki, MS,
  9. Liisa Toivanen, RN,
  10. Gabriele Vidgren, MS,
  11. Eva Tuomilehto-Wolf, MD,
  12. Christian Ehnholm, MD, PHD,
  13. Jillian Blaschak,
  14. Carl D Langefeld, MS,
  15. Richard M Watanabe, PHD,
  16. Victoria Magnuson, PHD,
  17. Delphine S Ally, MS,
  18. William A Hagopian, MD, PHD,
  19. Edna Ross,
  20. Thomas A Buchanan, MD,
  21. Francis Collins, MD, PHD and
  22. Michael Boehnke, PHD
  1. Genetic Epidemiology and Diabetes Unit, Department of Epidemiology and Health Promotion, National Public Health Institute Helsinki, Finland
  2. Department of Biochemistry, National Public Health Institute Helsinki, Finland
  3. Department of Physiology and Biophysics, Division of Endocrinology, University of Southern California Los Angeles, California
  4. School of Medicine, and the Department of Medicine, Division of Endocrinology, University of Southern California Los Angeles, California
  5. National Human Genome Research Institute, National Institutes of Health Maryland, Bethesda
  6. Department of Biostatistics, School of Public Health, University of Michigan Michigan, Ann Arbor
  7. Department of Medicine, University of Washington Seattle, Washington
  1. Address correspondence and reprint requests to Dr. Timo Valle, National Public Health Institute, Department of Epidemiology and Health Promotion, Genetic Epidemiology and Diabetes Unit, Mannerheimintie 166, SF-00300 Helsinki, Finland. E-mail: timo.valle{at}ktl.fi

Abstract

OBJECTIVE To map and identify susceptibility genes for NIDDM and for the intermediate quantitative traits associated with NIDDM.

RESEARCH DESIGN AND METHODS We describe the methodology and sample of the Finland-United States Investigation of NIDDM Genetics (FUSION) study. The whole genome search approach is being applied in studies of several different ethnic groups to locate susceptibility genes for NIDDM. Detailed description of the study materials and designs of such studies are important, particularly when comparing the findings in these studies and when combining different data sets.

RESULTS Using a careful selection strategy, we have ascertained 495 families with confirmed NIDDM in at least two siblings and no history of IDDM among the first-degree relatives. These families were chosen from more than 22,000 NIDDM patients, representative of patients with NIDDM in the Finnish population. In a subset of families, a spouse and offspring were sampled, and they participated in a frequently sampled intravenous glucose tolerance test (FSIGT) analyzed with the Minimal Model. An FSIGT was completed successfully for at least two nondiabetic offspring in 156 families with a confirmed nondiabetic spouse and no history of IDDM in first-degree relatives.

CONCLUSIONS Our work demonstrates the feasibility of collecting a large number of affected sib-pair families with NIDDM to provide data that will enable a whole genome search approach, including linkage analysis.

  • Received April 30, 1997.
  • Accepted February 26, 1998.
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