The Zuni Pueblo, in NM, is home to a small, geographically isolated, tribe, which has been relatively endogamous for hundreds of years. The Zuni Pueblo is currently experiencing a major epidemic of renal disease. This epidemic, unlike those in other American Indian communities, is attributable to high rates of diabetic and non-diabetic renal disease. Mesangiopathic nephropathy, most commonly IgA nephropathy (IgAN), comprises the majority of non-diabetic renal disease. Almost everyone at Zuni has a relative with renal disease, leading to strong community support for collaborative research. This has created a unique opportunity to identify genetic and environmental factors that modulate the susceptibility to renal disease and intermediate phenotypes. To maximize this opportunity, we established the, NIDDK funded, Zuni Kidney Project (ZKP). We have conducted a population-based survey of Zuni residents 5 years of age. We have ascertained family structure, quantified glycemic control, proteinuria, and renal function, and isolated DNA in over 1,650 participants. The ZKP is participating in FIND, a NIDDK funded sib pair-based consortium charged with identifying diabetic nephropathy susceptibility genes. However, the study design and ascertainment criteria in FIND do not take advantage of the unique population structure of Zuni. This has limited the ZKP's involvement in FIND and led to under-utilization of this unique resource. The present application requests support to conduct a study of extended families to identify genomic segments that modulate susceptibility to diabetic and non-diabetic renal disease and intermediate phenotypes. We will identify risk factors that show the strongest evidence for single gene effects and map those genes to specific chromosomal regions. Our investigative team includes the Zuni Pueblo, University of New Mexico Health Sciences Center (UNMHSC), and Southwest Foundation for Biomedical Research, and Strong Heart Study.
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