The Family Investigation of Nephropathy and Diabetes (FIND) Design and methods

On behalf of the Family Investigation of Nephropathy and Diabetes Research Group,; Knowler, William C.; Coresh, Josef; Elston, Robert C.; Freedman, Barry I.; Iyengar, Sudha K.; Kimmel, Paul L.; Olson, Jane M.; Plaetke, Rosemarie; Sedor, John R.; Seldin, Michael F.

doi:10.1016/j.jdiacomp.2003.12.007

« PreviousJournal of Diabetes and Its Complications
Volume 19, Issue 1 , Pages 1-9, January 2005

The Family Investigation of Nephropathy and Diabetes (FIND)

Design and methods

On behalf of the Family Investigation of Nephropathy and Diabetes Research Group
- The members are listed in Appendix.
William C. Knowler
- Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
Josef Coresh
- Department of Epidemiology Biostatistics and Medicine, Johns Hopkins University, Baltimore MD, USA
Robert C. Elston
- Corresponding author. Tel.: +1-216-778-3863; fax: +1-216-778-3280
- Department of Genetic Epidemiology and Biostatistics, MetroHealth Medial Center, Case Western Reserve University, 2500 MetroHealth Drive, Rammelkamp 258, Cleveland, OH 44109, USA
Barry I. Freedman
- Department of Internal Medicine—Nephrology, Wake Forest University, Winston-Salem, NC, USA
Sudha K. Iyengar
- Department of Genetic Epidemiology and Biostatistics, MetroHealth Medial Center, Case Western Reserve University, 2500 MetroHealth Drive, Rammelkamp 258, Cleveland, OH 44109, USA
Paul L. Kimmel
- Diabetic Nephropathy and HIV Programs, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA
Jane M. Olson
- Department of Genetic Epidemiology and Biostatistics, MetroHealth Medial Center, Case Western Reserve University, 2500 MetroHealth Drive, Rammelkamp 258, Cleveland, OH 44109, USA
Rosemarie Plaetke
- Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA
John R. Sedor
- Rammelkamp Center for Research and Education, Case Western Reserve University, Cleveland, OH, USA
Michael F. Seldin
- Department of Biological Chemistry and Medicine, University of California, Davis, Davis, CA, USA

Received 25 June 2003; received in revised form 20 December 2003; accepted 31 December 2003.

Abstract

Background

The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case–control study using mapping by admixture linkage disequilibrium (MALD).

Methods

In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits.

Two types of MALD studies are being done. One is a case–control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case–control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data.

Conclusions

Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention.

Keywords: Nephropathy, Diabetes, Genetics, Linkage, Admixture