A Large Set of Finnish Affected Sibling Pair Families With Type 2 Diabetes Suggests Susceptibility Loci on Chromosomes 6, 11, and 14

  1. Kaisa Silander1,
  2. Laura J. Scott2,
  3. Timo T. Valle3,
  4. Karen L. Mohlke1,
  5. Heather M. Stringham2,
  6. Kerry R. Wiles1,
  7. William L. Duren2,
  8. Kimberly F. Doheny4,
  9. Elizabeth W. Pugh4,
  10. Peter Chines1,
  11. Narisu Narisu1,
  12. Peggy P. White2,
  13. Tasha E. Fingerlin2,
  14. Anne U. Jackson2,
  15. Chun Li2,
  16. Soumitra Ghosh1,
  17. Victoria L. Magnuson1,
  18. Kimberly Colby1,
  19. Michael R. Erdos1,
  20. Jason E. Hill1,
  21. Pablo Hollstein1,
  22. Kathleen M. Humphreys1,
  23. Roshni A. Kasad1,
  24. Jessica Lambert1,
  25. Konstantinos N. Lazaridis1,
  26. George Lin1,
  27. Anabelle Morales-Mena1,
  28. Kristin Patzkowski1,
  29. Carrie Pfahl1,
  30. Rachel Porter1,
  31. David Rha1,
  32. Leonid Segal1,
  33. Yong D. Suh1,
  34. Jason Tovar1,
  35. Arun Unni1,
  36. Christian Welch1,
  37. Julie A. Douglas2,
  38. Michael P. Epstein2,
  39. Elizabeth R. Hauser2,
  40. William Hagopian5,
  41. Thomas A. Buchanan6,
  42. Richard M. Watanabe27,
  43. Richard N. Bergman8,
  44. Jaakko Tuomilehto39,
  45. Francis S. Collins1 and
  46. Michael Boehnke2
  1. 1Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland
  2. 2Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan
  3. 3Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland
  4. 4Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
  5. 5Pacific Northwest Research Institute, Seattle, Washington
  6. 6Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
  7. 7Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
  8. 8Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
  9. 9Department of Public Health, University of Helsinki, Helsinki, Finland
  1. Address correspondence and reprint requests to Michael Boehnke, PhD, Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor, Michigan 48109-2029. E-mail: boehnke{at}umich.edu

Abstract

The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS] = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION 1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at 58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152 cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1 + 2 sample.

Footnotes

    • Accepted December 4, 2003.
    • Received July 21, 2003.
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  1. doi: 10.2337/diabetes.53.3.821 Diabetes March 2004 vol. 53 no. 3 821-829
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