EXTENDED FAMILY INVESTIGATION OF NEPHROPATHY AND DIABETES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。糖尿病肾病家族调查(FIND)研究旨在利用一致性和非一致性同胞配对分析方法定位糖尿病肾病的基因。我们是11个参与调查中心之一(见图)[圣安东尼奥PIC的阿布博士阁下]，招募墨西哥裔美国人家庭。在这个方案中，我们将通过招募50个扩展的、多基因的家系来扩大我们的发现家系，以便用方差成分分析的方法来寻找糖尿病肾病基因。除了遗传学研究外，我们还将制定和实施一种方法，以加强受试者在知情和自愿的情况下参与遗传家庭研究。我们目前的研究将从几个方面补充FIND研究：(1)登记和收集目前被排除在FIND研究之外的家庭成员的数据，这将增加与FIND连锁分析相关的样本量和能力，(2)使用方差分量分析(VCA)搜索糖尿病肾病基因，与FIND建议的分析方法(协调和不一致的亚对)相反。这项研究将(1)确定并招募50个Find先证者的一、二、三级亲属的多重家庭；(2)所有已登记的Find先证者亲属的2型糖尿病和糖尿病肾病(DN)的表型；(3)加强受试者对遗传家系研究(GFS)的知情和自愿参与，特别强调提高对与参与GFS相关的风险和伦理问题的认识；(4)使用方差成分分析(VCA)技术研究糖尿病肾病的遗传学。整个项目需要四年时间才能完成，分两个阶段进行。在第一阶段(两年)，我们将联系和招募寻找延伸亲属，对所有登记的亲属进行表型，并制定一种方法，提高受试者在知情和自愿参与GFS方面的能力。在第二阶段，我们将进行基因组扫描/连锁。目的：该项目的主要目标是通过招募50名亲属来扩大参加肾病和糖尿病家族调查(FIND)的家庭，以便使用方差成分连锁方法评估糖尿病肾病(DN)的易感基因及其相关表型。具体目标：(1)确定并登记50个寻找先证者一、二、三级亲属的多重家庭。(2)2型糖尿病(T2 DM)和糖尿病肾病(DN)先证者的表型登记亲属。(3)加强受试者在知情和自愿的情况下参与遗传家系研究。(4)用方差成分分析(VCA)技术研究糖尿病肾病的遗传学。意义：登记和收集目前被排除在FIND研究之外的大家庭成员的数据，将增加与FIND连锁分析和其他相关项目相关的样本规模和力量。此外，我们计划在单变量和多变量条件下检查糖尿病肾病及其相关的表型(例如，GFR)。与基于同胞对的FIND调查相比，基于系谱的方差分量方法非常适合于本研究中提出的调查。将互补设计应用于糖尿病肾病的研究将提高我们对糖尿病和糖尿病肾病等复杂疾病的遗传学基础的理解。

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 Family Investigation of Nephropathy of Diabetes (FIND) Study aims to localize genes for DN using concordant and discordant sibpair analytical approach. We are one of 11 participating Investigation Centers (PICs) [Dr. H.E. Abboud, PI of the San Antonio PIC), enrolling families of Mexican American origin. In this proposal, we will expand our FIND families by enrolling 50 extended, multiplex families in order to search for DN genes with variance components analysis approach. In addition to the genetic study, we will develop and implement a method to enhance subjects' informed and voluntary participation in genetic family studies. Our current study will complement the FIND study in several ways: (1) enroll and collect data on family members who are currently excluded from the FIND study, which will increase sample size and power related to FIND linkage analysis, (2) search for DN genes with variance components analysis (VCA), contrarily to the FIND proposed analytical approach (concordant and discordant subpair). This study will (1) Identify and enroll 50 multiplex families of FIND probands' first, second and third degree relatives; (2) Phenotype all enrolled relatives of FIND probands regarding type 2 diabetes and diabetic nephropathy (DN); (3) Enhance subjects' informed and voluntary participation in genetic family studies (GFS), with special emphasis on improving awareness of risks and ethical issues associated with their participation in GFS; (4) Investigate the genetics of DN by using variance components analysis (VCA) techniques. The entire project will require four years to complete and will be conducted in two phases. In the first phase (2 years), we will contact and enroll FIND extended relatives, phenotype all enrolled relatives and develop a method to enhance subjects' informed and voluntary participation in GFS. In Phase 2, we will perform genome scan/linkage. Objective: The project's main objective is to expand families enrolled in the Family Investigation of Nephropathy and Diabetes (FIND) families by enrolling 50 extended relatives in order to assess susceptibility genes for diabetic nephropathy (DN) and its related phenotypes using a variance components linkage approach. Specific aims: (1) Identify and enroll 50 multiplex families of FIND probands' 1st, 2nd, and 3rd degree relatives. (2) Phenotype enrolled relatives of FIND probands regarding type 2 diabetes (T2DM) and diabetic nephropathy (DN). (3) Enhance subjects' informed and voluntary participation in genetic family studies (GFS). (4) Investigate the genetics of DN by using variance components analysis (VCA) techniques. Significance: The enrollment and collection of data on extended family members, who are currently excluded from the FIND study, will increase sample size and power related to the FIND linkage analysis and other related projects. Additionally, we plan to examine DN and its correlated phenotypes (e.g., GFR) in both univariate and multivariate terms. The pedigree-based variance components approach is very appropriate for the investigations proposed in this study in comparison with the sibpair-based FIND investigations. An application of a complementary design to the search for DN will improve our understanding of the genetic basis of complex diseases such as diabetes and DN.