EXTENDED FAMILY INVESTIGATION OF NEPHROPATHY AND DIABETES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。糖尿病肾病家系调查（FIND）研究的目的是使用一致和不一致同胞分析方法定位DN的基因。我们是11个参与研究中心（PIC）之一[H. E. Abboud，圣安东尼奥PIC的PI），招募墨西哥裔美国人家庭。在本研究中，我们将通过招募50个扩展的多重家族来扩大我们的FIND家族，以便使用方差成分分析方法来寻找DN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族研究。我们目前的研究将以几种方式补充FIND研究：（1）招募和收集目前从FIND研究中排除的家族成员的数据，这将增加与FIND连锁分析相关的样本量和功效，（2）与FIND提出的分析方法（一致和不一致子对）相反，使用方差分量分析（VCA）搜索DN基因。本研究将（1）确定并招募50个FIND先证者的一级、二级和三级亲属的多重家族;（2）对FIND先证者所有招募的亲属进行2型糖尿病和糖尿病肾病（DN）的表型分析;（3）加强受试者在知情和自愿的情况下参与遗传家系研究，特别强调提高对参与GFS相关风险和伦理问题的认识;（4）采用方差成分分析（VCA）技术研究DN的遗传学。 整个项目将需要四年时间完成，并将分两个阶段进行。在第一阶段（2年），我们将联系并招募FIND的直系亲属，对所有招募的亲属进行表型分析，并开发一种方法来增强受试者知情和自愿参与GFS。在第二阶段，我们将进行基因组扫描/连接。 目的：该项目的主要目标是通过招募50名远亲来扩大肾病和糖尿病家庭调查（FIND）家庭的成员，以便使用方差分量连锁方法评估糖尿病肾病（DN）及其相关表型的易感基因。具体目标：（1）确定并招募50个FIND先证者的一级、二级和三级亲属的多重家族。(2)表型研究招募了2型糖尿病（T2 DM）和糖尿病肾病（DN）FIND先证者的亲属。(3)加强受试者知情和自愿参与遗传家族研究（GFS）。(4)应用方差成分分析（VCA）技术探讨DN的遗传学特征。 重要性：目前从FIND研究中排除的大家庭成员的入组和数据收集将增加与FIND连锁分析和其他相关项目相关的样本量和把握度。此外，我们计划检查DN及其相关表型（例如，GFR）单变量和多变量项。与基于同胞对的FIND调查相比，基于家系的方差分量方法非常适合本研究中提出的调查。应用互补设计寻找DN将提高我们对复杂疾病如糖尿病和DN的遗传基础的理解。

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.