This Program Project supports the San Antonio Family Heart Study, the first comprehensive genetic epidemiological study of atherosclerosis and its correlates in Mexican Americans. Its goal is to detect and map new polymorphic genes that influence variation in susceptibility to cardiovascular disease (CVD) in Mexican Americans. Because non-insulin-dependent diabetes mellitus (NIDDM) and obesity are risk factors for CVD and are common in this population, the pleiotropic effects of diabetes-and obesity- related genes on quantitative correlates of CVD also will be studies. By the end of the current grant period nearly 1,400 individuals in more than 40 extended Mexican American families will have been recruited and examined. Major genes already have been detected that influence HDL cholesterol, LDL, cholesterol, apolipoprotein AI (apoAI), apoB, three obesity-related measures (fat mass, body mass index, and an indicator of bioresistance), two NIDDM-related traits (two hour post-challenge insulin and diabetes age at onset), and two hormonal measures (sex hormone biding globulin an dehydroepiandrosterone sulfate). The first priority in the proposed grant period will be to map these major genes by genomic searching, using powerful penetrance-based and variance component analyses with genotypic data for 391 highly polymorphic markers spaced approximately 10 centimorgans apart. In a recall of 750 San Antonio Family Heart Study participants in the proposed grant period, a more complete risk factor profile will be developed by measuring quantitative phenotypes related to fibrinolysis and thrombosis, and phenotypes closer to the atherosclerotic vascular disease endpoint will be assessed by measuring carotid artery wall thickness. Statistical evidence for major genes will be sought with the goal of mapping genes that have substantial effects on these phenotypes, using the same battery of highly polymorphic markers. Strong evidence for linkage to a specific chromosomal region will be pursued using the positional candidate approach.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Southwest Foundation for Biomedical Research
San Antonio
United States
Zip Code
Konigorski, Stefan; Wang, Yuan; Cigsar, Candemir et al. (2018) Estimating and testing direct genetic effects in directed acyclic graphs using estimating equations. Genet Epidemiol 42:174-186
Espin-Garcia, Osvaldo; Craiu, Radu V; Bull, Shelley B (2018) Two-phase designs for joint quantitative-trait-dependent and genotype-dependent sampling in post-GWAS regional sequencing. Genet Epidemiol 42:104-116
Chien, Li-Chu; Chiu, Yen-Feng (2018) General retrospective mega-analysis framework for rare variant association tests. Genet Epidemiol 42:621-635
Ning, Chao; Kang, Huimin; Zhou, Lei et al. (2017) Performance Gains in Genome-Wide Association Studies for Longitudinal Traits via Modeling Time-varied effects. Sci Rep 7:590
Kulkarni, Hemant; Mamtani, Manju; Wong, Gerard et al. (2017) Genetic correlation of the plasma lipidome with type 2 diabetes, prediabetes and insulin resistance in Mexican American families. BMC Genet 18:48
Mamtani, Manju; Kulkarni, Hemant; Wong, Gerard et al. (2016) Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts. Lipids Health Dis 15:67
Kulkarni, Hemant; Mamtani, Manju; Peralta, Juan Manuel et al. (2016) Lack of Association between SLC30A8 Variants and Type 2 Diabetes in Mexican American Families. J Diabetes Res 2016:6463214
Hanson, Robert L; Leti, Fatjon; Tsinajinnie, Darwin et al. (2016) The Arg59Trp variant in ANGPTL8 (betatrophin) is associated with total and HDL-cholesterol in American Indians and Mexican Americans and differentially affects cleavage of ANGPTL3. Mol Genet Metab 118:128-37
Mamtani, Manju; Kulkarni, Hemant; Dyer, Thomas D et al. (2016) Genome- and epigenome-wide association study of hypertriglyceridemic waist in Mexican American families. Clin Epigenetics 8:6
Kumar, Satish; Curran, Joanne E; Glahn, David C et al. (2016) Utility of Lymphoblastoid Cell Lines for Induced Pluripotent Stem Cell Generation. Stem Cells Int 2016:2349261

Showing the most recent 10 out of 258 publications