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 sets of families as well as case-control sets with well-characterized diabetic nephropathy (DN), establish a secure master database, and to localize and identify genes that influence susceptibility to diabetic nephropathy and end-stage renal disease. The FIND has recruited European American (EA), African American (AA), Mexican American (MA) and American Indian (AI) populations to assess genetic contributions that may be specific to various populations. Genetic strategies include genome-wide linkage analyses and mapping by admixture linkage disequilibrium (MALD). In addition, most of the clinical centers conduct a separate sub-study for diabetic retinopathy. In the years of the recruitment phase for both the family and case-control studies the FIND study screened more than 9500 participants. Phenotype data include a medical record review, a self-reported medical questionnaire and biological samples (blood and urine) for biochemical assay. B-lymphocytes, serum, plasma and urine have been preserved in an archive for future studies. Data cleaning for this project relied heavily on the S.A.G.E. programs RELTEST, to verify pedigree relationships, and MARKERINFO, to identify Mendelian-incompatible genotyping errors. A genomewide linkage scan, using the regression-based approach in the SIBPAL program in S.A.G.E., the conditional logistic model in LODPAL and other methods, was completed in more than 4800 participants from the family study. A low-density association analysis was also carried out via the family-based method implemented in ASSOC. Manuscripts reporting findings on diabetes mellitus and on DN and several related traits are currently under review. The AA MALD study recently published results from its first analysis in Nature Genetics. Identification of genes that influence susceptibility to diabetic nephropathy and/or kidney failure 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 performing genotyping for a genomewide association study in 5200 individuals, including some nuclear families. Data analysis of the results will be performed in the spring of 2009, with ASSOC as the primary analysis approach for the samples including family data.
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