The Hypertension Genetic Epidemiology Network (HyperGEN) is a multicenter family study in which African American and Caucasian sibships, each with 2 or more hypertensive sibs, were recruited from five population based studies. Genetic markers include a genome-wide linkage scan with nearly 400 microsatellites, and a genome-wide association study (GWAS), in addition to candidate genes. The Family Blood Pressure Program (FBPP) is a collaborative endeavor among four independently established multicenter studies such as HyperGEN with the same scientific goals. The four FBPP Networks are the GenNet, GENOA, HyperGEN, and SAPPHIRe. The FBPP provides unprecedented opportunities with one of the largest sample sizes (13,500 participants), and spans four ethnic groups [African Americans , non-Hispanic Whites , Mexican- Americans, and Asians.
The HERITAGE is the only known family-based study of exercise intervention to evaluate the role of genes and sequence variants involved in the response to a physically active lifestyle. The intervention study design consists of 99 White families (229 males, 240 females) and 115 Black families (83 males and 141 females) with measurements at baseline visit and again after 20 weeks of standardized and strictly supervised exercise training. There are over 18 trait domains (e.g. dietary, lipids and heparin, diabetes, steroids, CT scans, IVGTT etc), for a grand total of over one thousand variables at each visit. Marker data include a genome-wide linkage scan and GWAS, in addition to a large number of candidate genes.
The GenSalt is an intervention study of rural Chinese high blood pressure probands and their families with the goal of delineating the genes that regulate the effects of dietary sodium and potassium intake on blood pressure (BP) variability. Measurements were made at multiple time points during a 3-1/2 week period of dietary intervention. Urinary samples were taken at strategic intervals to ensure compliance with the protocol. The master database includes intervention data on the hypertensive proband and his/her siblings, spouse and offspring (N = 1,887). Marker data include about 400 genome-wide microsatellites, SNPs in candidate genes, and finally a GWAS.
The NHLBI Family Heart Study (FamHS) is a multicenter study with the primary goal of finding the genetic and nongenetic determinants of coronary heart disease (CHD), atherosclerosis and cardiovascular risk factors. The study design involved selecting 2,000 random individuals and 2,000 individuals with family histories of CHD from three population-based epidemiology studies. Family risk scores were computed using medical histories of the proband and their family members, and 657 families with the highest risk scores and 588 randomly sampled families were finally selected for extensive phenotyping and genotyping. The master database includes extensive information (e.g., ECGs, ultrasound, BP, lipids, lipoproteins, hemostatic factors and routine chemistries). In addition, a genome-wide linkage scan and GWAS marker data are also available.
GOLDN is a multi-center family pharmacogenetic study that is investigating gene- environment interactions on lipid profiles. 1,200 subjects in extended pedigrees were measured before and after two environmental exposures: 1) a dietary fat challenge to assess genetic regulators of fat uptake and clearance and 2) a 3 week clinical trial of fenofibrate to assess pharmacogenetic influences on response to treatment. The goals of the study are to identify and characterize genetic loci that predict the lipid profile treatment responses.
LLFS is a multi-center international family study of the genetics of longevity. 5,500 family members from pedigrees enriched for multiple exceptionally long lived individuals are clinically assessed in many major domains of health including cardiovascular, physical function, frailty, chronic conditions, mental acuity. Immortalized cell lines are created in the oldest generation. Genomic scans as well as denser typing in candidate gene regions are being done in all subjects. This unique resource provides an important platform for much future research on the genetics of healthy aging and longevity.
Mentored research projects using adminstrative data sets are used routinely as part of didactic coursework and are available to our trainees for research projects. Projects may access existing research datasets, administrative data, electronic health records (EHR), registries and other sources from WU, BJC HealthCare, and CADR, a resouce containing a variety of administrative data for clinical outcomes research including Medicare, Medicaid, SEER-Medicare, and Healthcare Cost and Utilization Project data and others. WU has electronic medical records for its outpatient facilities (Allscripts) which is being integrated with EHRs at BJH through a clinical data repository. Trainees can do pharmacoepidemiologic/pharmacoeconomic research in collaboration with investigators at St. Louis-based Express Scripts (a large pharmacy benefits management company that handles pharmacy-based administrative data for 60M people).
The dbGaP was developed to archive and distribute the results of studies that have investigated the interaction of genotype and phenotype. Large numbers of genetic and genomic studies supported especially by research funding from the NIH are providing access to their research data through the dbGaP to other investigators interested in exploring these data to answer important new hypotheses. Authorized users include the researchers who may request data sets for specific research uses, the institutional signing officials from the requesting investigator’s home organization who certify and submit such requests, and the NIH staff who review and process requests (e.g. members of the Data Access Committees).