Family Investigation Of Nephropathy And Diabetes Research Articles

Urine Exosomal MicroRNA Profiling in the Family Investigation of Nephropathy and Diabetes (FIND)

About 1 in 3 adults with either type 1 or type 2 diabetes (T2D) has some degree of renal injury or diabetic nephropathy (DN). There is a need to develop more sensitive and specific means of detecting and gauging DN progression so that therapies can be started as early as possible. We hypothesized that UE microRNAs (miRs), small, non-coding 21-25 nucleotide species, a relatively stable readout of renal metabolic health, could be utilized in this fashion. From the NIH, NIDDK Central Repository, we obtained 299 urine samples (300 ml) from African American subjects previously enrolled in the FIND study. The FIND study was initially designed to elucidate genetic determinants of DN in related patient populations using both T2D and non-diabetic control (CTRL), male (M) and female (F) subjects. Our samples included: 20 CTRL-M, 46 CTRL-F, 43 T2D-M, and 90 T2D-F). Other deidentified demographic and clinical data was obtained from the NIH. We measured urine albumin and creatinine in the samples and calculated ratios (mg albumin/g creatinine). Patients were categorized as normal (N, < 30, 120 subjects), microalbuminuric (MIC, 30-300, 33 subjects), or macroalbuminuric (MAC, >300, 46 subjects). Urine exosomes (UE) were isolated from each urine using the Total Exosome Isolation (from urine) kit (Thermofisher), which allows for precipitation of water-insoluble exosomes via centrifugation at medium speed (10,000g) for 1 hour. Small RNA was isolated followed by cDNA synthesis using commercially-available kits (Qiagen). Previously, we found miR-451a to be more highly expressed in UE from human subjects with chronic kidney disease, than in control subjects. We also found this miR to be a potential predictive biomarker for albuminuria in diabetic rats. Therefore, first we used conventional qRT-PCR to evaluate UE levels of miR-451a, as well as, the anti-sense product, miR-451b. MiR-127 was used as the internal standard, as it has been reported not to change with T2D. In MAC subjects, we found that the UE median miR-451a level increased with a fold change (FC) of 3.5 (relative to N). Similarly, miR-451b showed a 3.6-fold increase. FC in the MIC groups were 2.9 and 2.5 for miR-451a and b, respectively (relative to N). Next we conducted an unbiased screen of commonly excreted miRs in these subjects using a miR Array (miRCURY LNA miRNA Focus PCR panel, Qiagen) configured with 88 targets highly expressed in UE. We screened 19 subjects representing a range of conditions, i.e., albuminuric and normal, diabetic and non-diabetic, male and female. We found positive signals in 5 or more subjects for 16 miRs. Of those, 12, i.e., let-7b-5p, miR-16-5p, miR-23b-3p, miR-26a-5p, miR-27a-3p, miR-30a-5p, miR-30b-5p, miR-30c-5p, miR30e-5p, miR-141-3p, miR-203a, and miR-204-5p were expressed at mean levels 2-fold higher in MAC versus N subjects. Furthermore, 13 of these miRs were also over 2-fold higher when subjects were divided as T2D versus CTRL, i.e., the above list plus miR-200c-3p and miR-30d-5p, but not let-7b-5p in this case. When subjects were not divided by groups, miR-598-5p had the highest positive correlation with urinary albumin excretion, R = 0.53 and p = 0.035 (for slope ≠ 0). Using miRNet (McGill University), a freely available miR analysis software tool, we mined for common targets of miR-451(a & b) and miR-598. One putative target of both miR-451b and miR-598 was vascular endothelial growth factor A (VEGFA), which has been shown to play a role in DN. In sum, these miRs represent candidate targets to undergo additional scrutiny. We conclude UE miRs may hold clinical value in the non-invasive assessment of DN severity and predicting progression. NIH/NINDS U01-DK103225 (Feldman, PI); Ecelbarger Pilot. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).

BackgroundThe presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample.ResultsA fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy.ConclusionsThe identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2654-x) contains supplementary material, which is available to authorized users.

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

A Genome-Wide Search for Linkage of Estimated Glomerular Filtration Rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

ObjectiveEstimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR.MethodsGenome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula.ResultsThe non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4×10−5) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5×10−4) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5×10−4) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome.ConclusionThe present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

Genetic Association and Gene-Gene Interaction Analyses in African American Dialysis Patients With Nondiabetic Nephropathy

African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1. The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 × 10(-7)) with replication in FIND (P = 5.0 × 10(-21) and 1.9 × 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001). Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.

Genetic analysis of albuminuria in aging mice and concordance with loci for human diabetic nephropathy found in a genome-wide association scan

Aging in the kidney can cause albuminuria, and discovering molecular mechanisms responsible for this might offer a new perspective on the etiology of this abnormality. Haplotype association mapping in the mouse is a novel approach which uses the haplotypes of the relatively closely related mouse inbred strains and the phenotypic variation among these strains to find associations between haplotypes and phenotype. The albumin-to-creatinine ratios, a measure of urinary albumin excretion, were determined in 30 inbred mouse strains at 12, 18, and 24 months of age. Mapping was performed for males and females separately at all three time points using a high density set of 63,222 single-nucleotide polymorphisms to determine genetic loci involved in albuminuria. One significant and eight suggestive loci were found, some of which map to previously identified loci for traits associated with kidney damage in the mouse, but with a much higher resolution thus narrowing their chromosomal location. These nine loci were then compared with genome-wide association scans for diabetic nephropathy (DN) in human type I diabetes. Our study found that two of the nine mouse loci for age-related albuminuria were significantly associated with DN and consistent across male and female strata. This suggests common underlying genes predispose to kidney disease in mice and humans.

Preferences regarding Genetic Research Results: Comparing Veterans and Nonveterans Responses

Objective: Communicating genetic research results to participants presents ethical challenges. Our objectives were to examine participants’ preferences in receiving future genetic research results and to compare preferences reported by veteran and nonveterans participants. Methods: Secondary analysis was performed on data collected in 2000–2004 from 1,575 consent forms signed by Mexican-American participants enrolled in 2 genetic family studies (GFS) in San Antonio: The Family Investigation of Nephropathy and Diabetes (FIND) and the Extended FIND (EFIND). The consent forms for these studies contained multiple-choice questions to examine participants’ preferences about receiving their (1) clinical lab results and (2) future genetic research results. The FIND and EFIND databases had information on subjects’ demographic characteristics and some selected clinical variables. We identified veterans using the Veterans Health Administration’s (VHA’s) centralized data repository. We compared veterans’ and nonveterans’ preferences using Student’s t test for continuous variables and χ² test for discrete variables. A logistic regression analyzed subjects’ preference for receiving their research results, controlling for other socio-demographic and clinical variables. Results: The sample included 275 (18%) veterans and 1,247 (82%) nonveterans. Our results indicated a strong desire among the majority of participants 1,445 (95%) in getting their clinical lab research results. Likewise, 93% expressed interest in being informed about their future genetic results. There was no significant difference in veterans’ and nonveterans’ preference to disclosure of the research results (χ² test; p > 0.05). Regression analysis showed no significant relationship (p = 0.449) between the outcome (receiving research results) and veterans’ responses after controlling for demographics and educational levels. Conclusion: Participants believed they would prefer receiving their genetic research results. Veterans are similar to nonveterans in their preferences. Offering genetic research results to participants should be based on well defined and structured plans to enhance interpretation of genetic data.

Genome-wide scan for estimated glomerular filtration rate in multi-ethnic diabetic populations: the Family Investigation of Nephropathy and Diabetes (FIND).

Diabetic nephropathy, the most common cause of end-stage renal disease, aggregates in families and specific ethnic groups. Deconstructing diabetic nephropathy into intermediate, quantitative phenotypes may increase feasibility of detecting susceptibility loci by genetic screens. Glomerular filtration rate (GFR), which characterizes diabetic nephropathy, was employed as a quantitative trait in a preliminary whole-genome scan. Estimated GFR (eGFR) was calculated for 882 diabetic sibpairs (mean age 57 years) of African-American (25.6% of total), American Indian (8.6%), European-American (14.2%), and Mexican-American (51.6%) descent enrolled in the initial phase of the Family Investigation of Nephropathy and Diabetes (FIND). A whole-genome scan was performed using 404 microsatellite markers (average spacing 9 cM) and model-free linkage analysis. For all ethnicities combined, strong evidence for linkage was observed on chromosomes 1q43 (P = 3.6 x 10(-3)), 7q36.1 (P = 2.1 x 10(-4)), 8q13.3 (P = 4.6 x 10(-4)), and 18q23.3 (P = 2.7 x 10(-3)). Mexican-American families, who comprised the major ethnic subpopulation in FIND, contributed to linkage on chromosomes 1q43, 2p13.3, 7q36.1, 8q13.3, and 18q23.3, whereas African-American and American-Indian families displayed linkage peaks on chromosomes 11p15.1 and 15q22.3, respectively. We have demonstrated multiple chromosomal regions linked to eGFR in a multi-ethnic collection of families ascertained by a proband with diabetic nephropathy. Identification of genetic variants within these loci that are responsible for the linkage signals could lead to predictive tests or novel therapies for subsets of patients at risk for diabetic nephropathy.

Genome-Wide Scans for Diabetic Nephropathy and Albuminuria in Multiethnic Populations

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.

Diabetes and the Kidney

Diabetes and the Kidney

Ethical Issues Associated with Conducting Genetic Family Studies of Complex Disease

To examine subjects' recognition of the risks and ethical issues associated with enrollment in genetic family studies (GFS) and explore how this recognition affects their informed and voluntary participation. A cross-sectional study design including both quantitative and qualitative data was employed. Structured interviews using the Contextual Assessment Approach Questionnaire (CAA-Q) were conducted with 246 Mexican American (MA) participants. To gain in-depth understanding of questionnaire responses, semi-structured interviews with 30 participants were conducted. All participants were interviewed before their enrollment in the Family Investigation of Nephropathy and Diabetes (FIND). Subjects' average age was 56 years; 62% were females. Seventy-eight percent of participants were not formally educated beyond high school and 72% reported an annual household income of < or =20,000 dollars. Eighty-five percent agreed to provide researchers with information on relatives' ages, gender, and education. Sixty-five percent of participants were willing to provide identifiable information such as names, addresses, and phone numbers of relatives. Sixty-three percent of participants indicated that there were direct benefits (i.e., supporting research) to disclosing relatives' information. Seventy-six percent stated that there were no risks associated with participation in GFS (e.g., discrimination or confidentiality of genetic information) compared with 10% who said that there were such risks. While discussing potential risks, subjects did not consider these to influence their decision to participate. Subjects enrolled in GFS did not recognize and tended to underestimate the social and cultural risks associated with their participation in GFS. If subjects do not fully comprehend the risks, this raises questions concerning their ability to provide informed consent and to voluntarily participate. We propose a subject-centered approach that views enrollment as an active process in which subjects and recruiters give and receive information on risks and ethical issues related to participation, which enhances protection of the rights and welfare of subjects participating in GFS.

The Family Investigation of Nephropathy and Diabetes (FIND)Design and methods

The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case–control study using mapping by admixture linkage disequilibrium (MALD). In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits. Two types of MALD studies are being done. One is a case–control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case–control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data. Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention.

The Family Investigation of Nephropathy and Diabetes (FIND): Design and methods

Background The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case–control study using mapping by admixture linkage disequilibrium (MALD). Methods In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits. Two types of MALD studies are being done. One is a case–control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case–control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data. Conclusions Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention.

Genetic determinants of diabetic nephropathy: The family investigation of nephropathy and diabetes (FIND).

Diabetes mellitus is the leading cause of ESRD in the United States. Family-based studies and segregation analyses suggest that inherited factors play a major role in susceptibility to diabetic renal complications, including albuminuria and chronic kidney failure. The Family Investigation of Nephropathy and Diabetes (FIND) study is a multicenter consortium established by the National Institute of Diabetes, Digestive and Kidney Diseases to identify the gene(s) responsible for diabetic nephropathy. Eight participating centers will enroll nearly 10,000 individuals by September 2004. Two independent strategies to detect causative genes will be used. These include family-based linkage analyses in African-American, American-Indian, Mexican-American, and European-American families (predominantly affected and discordant relative pair analyses) and mapping by admixture linkage disequilibrium (MALD) in African and Mexican Americans. Cell lines are being created from participants, and a repository containing stored urine and serum samples has been developed. This paper describes the enrollment criteria and methods used in FIND to allow for the detection of gene(s) predisposing to diabetic nephropathy.

Familial Clustering of Diabetic Nephropathy: Perceptions and Risk Recognition Among Mexican-American Patients With a Family History of Diabetes

Abstract Objective. Diabetic nephropathy (DN) clusters in families with type 2 diabetes, suggesting a genetic susceptibility for its development and progression. We investigated DN probands’ and relatives’: 1) perceptions of the causes and clustering of DN and 2) recognition of their genetic susceptibility and of other selected risk factors. Research methods. Structured interviews were conducted with 246 Mexican-American participants in the Family Investigation of Nephropathy and Diabetes (FIND) study using the Contextual Assessment Approach Questionnaire (CAA-Q). A total of 105 (43%) DN probands and 141 (57%) first-degree relatives were enrolled. Subjects averaged 56 years of age (range: 33–76; SD: 9.04); 62% were females. Data analysis included both qualitative and quantitative methods using Atlas.ti and SPSS 9.0 software packages. Results. Eighty-three percent of subjects recognized that type 2 diabetes clusters in their family, while 63% asserted that DN did not. Fifty-three percent of diabetic relatives presented with a high urinary albumin/creatinine ratio (≥0.03) and were unaware of having DN (P ≤0.05). All subjects viewed DN as a component of type 2 diabetes and not a separate disease entity. More than 80% of the subjects considered ethnicity but not age of onset or sex as risk factors for developing type 2 diabetes or DN. Conclusion. Participants viewed type 2 diabetes and DN in the context of health behaviors related to their everyday activities. They considered DN to be part of diabetes with no direct genetic predisposition and not a separate entity. Diabetic relatives under-estimated their risks for developing DN and were not engaged in preventive measures to reduce these risks. We recommend that health professionals consider these findings when interacting with high-risk diabetic patients. DN is a serious complication of diabetes that requires special care, education, prevention, and management.

Incorporating the Contextual Assessment Approach to regimens used in genetic family studies

Purpose: To develop a procedure that enhances enrollment and addresses ethical issues associated with participation in genetic family studies.Methods: The Contextual Assessment Approach (CAA) was standardized to the recruitment procedures in the Family Investigation of Nephropathy and Diabetes (FIND) study at the University of Texas Health Science Center at San Antonio. Structured interviews with the CAA questionnaire (CAA-Q) were conducted with 50 low-income Mexican-American probands. The CAA allows systematic interpretation of health beliefs, family dynamics, and attitudes regarding participation in FIND. Data analyses included qualitative and quantitative methods.Results: CAA analyses of probands' perspectives regarding relatives' enrollment in FIND facilitated recruiting 34 probands from whom 30 families were enrolled (family enrollment rate: 88%). CAA reduced recruitment efforts by 32% and avoided exerting undue pressure on unwilling participants to ensure voluntary participation. Remarkably, 76% of the subjects were unaware of any risk associated with participation in genetic family studies.Conclusions: Administering the CAA-Q before enrolling subjects in FIND increased our enrollment rate by targeting efforts toward the willing subjects and addressing ethical issues associated with their participation.