EXTENDED FAMILY INVESTIGATION OF NEPHROPATHY AND DIABETES

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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.