This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major goals of the Family Investigation of Nephropathy and Diabetes (FIND) study are to acquire families with well-characterized diabetic nephropathy (DN), as well as unrelated cases and controls, to establish a secure master database, and to localize and identify genes that influence susceptibility to DN and end-stage renal disease (ESRD). FIND has recruited European Americans (EA), African Americans (AA), Mexican Americans (MA) and American Indians (AI) to assess genetic contributions that may be specific to these populations. Analytical strategies include genomewide linkage analysis, genomewide association analysis and mapping by admixture linkage disequilibrium (MALD). In addition, most of the clinical centers conduct a separate sub-study for diabetic retinopathy. During the recruitment phase, the FIND study screened more than 9500 participants. Phenotype data include a self-reported medical questionnaire, a medical record review and biological samples (blood and urine) for biochemical assay. B-lymphocytes, serum, plasma and urine samples have been reserved in a repository for future studies. Data cleaning for this project has relied heavily on the S.A.G.E. programs RELTEST, to verify pedigree relationships, and on MARKERINFO, to identify Mendelian-incompatible genotyping errors. Several genomewide linkage scans using the regression-based approach in the S.A.G.E. program SIBPAL, the conditional logistic model in LODPAL and other methods, was completed in more than 4800 participants from the family study. A report of new linkage regions for type II diabetes mellitus was recently published, and manuscripts reporting new region and confirming previously implicated regions for DN and several measures of kidney function are currently under review. The AA MALD study identified a gene on chromosome 22, MYH9, associated with nondiabetic kidney disease. Identification of genes that influence susceptibility to DN and/or ESRD will lead to a better understanding of how serious kidney disease develops. This should eventually lead to improved treatment and prevention. Currently, the FIND study is completing initial analysis in a genomewide association study on 5200 mainly unrelated individuals from all four ethnic groups.
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