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Genome-Wide Scans for Diabetic Nephropathy and Albuminuria in Multi-Ethnic Populations: The Family Investigation of Nephropathy and Diabetes

¹FIND-Genetic Analysis and Data Coordinating Center; Department of Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, Ohio

Correspondence: ski{at}case.edu

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy (DN). Eleven centers participated under a single collection protocol to recruit large numbers of diabetic sib pairs concordant and discordant for DN. 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 DN in 397 sib pairs, as well as the quantitative trait urine albumin:creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the trait DN was on chromosomes 7q21.3, 10p15.3, 14q23.1 and 18q22.3. In ACR (883 diabetic sib pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1 and 15q26.3. These results confirm regions of linkage to DN 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 DN, a life-threatening complication of diabetes mellitus.

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