Genome-Wide Scans for Diabetic Nephropathy and Albuminuria in Multiethnic Populations

The Family Investigation of Nephropathy and Diabetes (FIND)

  1. Sudha K. Iyengar1,
  2. Hanna E. Abboud2,
  3. Katrina A.B. Goddard1,
  4. Mohammed F. Saad3,
  5. Sharon G. Adler4,
  6. Nedal H. Arar2,
  7. Donald W. Bowden5,
  8. Ravi Duggirala2,
  9. Robert C. Elston1,
  10. Robert L. Hanson6,
  11. Eli Ipp4,
  12. W.H. Linda Kao7,
  13. Paul L. Kimmel8,
  14. Michael J. Klag7,
  15. William C. Knowler6,
  16. Lucy A. Meoni7,
  17. Robert G. Nelson6,
  18. Susanne B. Nicholas3,
  19. Madeleine V. Pahl3,
  20. Rulan S. Parekh7,
  21. Shannon R.E. Quade1,
  22. Stephen S. Rich5,
  23. Jerome I. Rotter3,
  24. Marina Scavini9,
  25. Jeffrey R. Schelling10,
  26. John R. Sedor10,
  27. Ashwini R. Sehgal10,
  28. Vallabh O. Shah9,
  29. Michael W. Smith11,
  30. Kent D. Taylor3,
  31. Cheryl A. Winkler11,
  32. Philip G. Zager9,
  33. Barry I. Freedman5 and
  34. on behalf of the Family Investigation of Nephropathy and Diabetes Research Group*
  1. 1FIND-Genetic Analysis and Data Coordinating Center, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio
  2. 2University of Texas Health Science Center at San Antonio, San Antonio, Texas
  3. 3University of California, Los Angeles, California
  4. 4Harbor-University of California Los Angeles Medical Center, Los Angeles, California
  5. 5Wake Forest University, Winston-Salem, North Carolina
  6. 6National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
  7. 7Johns Hopkins University, Baltimore, Maryland
  8. 8National Institute of Diabetes and Digestive and Kidney Diseases program office, Bethesda, Maryland
  9. 9University of New Mexico, Albuquerque, New Mexico
  10. 10Case Western Reserve University, Cleveland, Ohio
  11. 11Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland
  1. Address correspondence and reprint requests to Dr. Sudha Iyengar, Department of Epidemiology and Biostatistics, Case Western Reserve University, Wolstein Research Building, Room no. 1315, 10900 Euclid Ave., Cleveland, OH 44106-7281. E-mail: ski{at}case.edu

Abstract

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 15 March 2007. DOI: 10.2337/db06-1154.

  • *

    * A complete list of the FIND Study Research Group is available in the appendix.

  • Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1154.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 20, 2007.
    • Received August 16, 2006.
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  1. Published online before print March 15, 2007, doi: 10.2337/db06-1154 Diabetes June 2007 vol. 56 no. 6 1577-1585
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