FAMILY INVESTIGATION OF NEPHROPATHY AND DIABETES (FIND)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肾病和糖尿病家族调查(FIND)研究的主要目标是获得具有良好特征的糖尿病肾病(DN)的家系集合和病例对照集合，建立安全的主数据库，并定位和识别影响糖尿病肾病和终末期肾病易感性的基因。该发现招募了欧洲裔美国人(EA)、非裔美国人(AA)、墨西哥裔美国人(MA)和美国印第安人(AI)群体，以评估可能针对不同群体的基因贡献。遗传策略包括全基因组连锁分析和利用混合连锁不平衡(MALD)进行定位。此外，大多数临床中心对糖尿病视网膜病变进行单独的子研究。在家庭研究和病例对照研究的招募阶段，FIND研究筛选了9500多名参与者。表型数据包括病历回顾、自我报告的医学问卷和用于生化分析的生物样本(血液和尿液)。B淋巴细胞、血清、血浆和尿液已保存在档案中，以供未来研究。该项目的数据清理在很大程度上依赖于S.A.G.E.程序RELTEST和MARKERINFO，RELTEST和MARKERINFO分别用于验证系谱关系和识别孟德尔不相容的基因分型错误。使用S.A.G.E.的SIBPAL程序中基于回归的方法、LODPAL中的条件Logistic模型和其他方法，对来自家庭研究的4800多名参与者进行了全基因组连锁扫描。通过在ASSOC中实施的基于家庭的方法，还进行了低密度关联分析。目前正在审查关于糖尿病、糖尿病肾病和几个相关特征的报告结果的手稿。AA MALD研究最近在《自然遗传学》上发表了它的第一次分析结果。识别影响糖尿病肾病和/或肾衰竭易感性的基因将有助于更好地了解严重的肾脏疾病是如何发展的。这最终将导致改善治疗和预防。目前，FIND研究正在对5200名个体进行全基因组关联研究的基因分型，其中包括一些核心家庭。结果的数据分析将在2009年春季进行，ASSOC是包括家庭数据在内的样本的主要分析方法。

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.