The objective of Project 1 is to map genes that influence quantitative phenotypes related to the development of atherosclerosis in Mexican American families in the San Antonio Family Heart Study. A genomic search, utilizing a 10 centimorgan map of 391 short tandem repeat markers distributed throughout the genome, will be conducted to determine the chromosomal locations of six major genes detected during the current grant period (gene influencing HDL-C,LDL-C, apoAI, apoB, SHBG, and DHEAS). For lipoprotein phenotypes for which no major genes have yet been detected, evidence for major gene effects will be sought. The genomic search will focus on chromosomal regions that show preliminary evidence for linkage in sibship based variance component screening tests in Project 2. If warranted, the analyses will be expand to include additional DNA markers in these regions. Genetic effects on carotid and fibrinolysis phenotypes will be quantified using data from a recall of 750 family members. Full pedigree variance component analysis as well as penetrance-based methods will be used in a genomic search to determine the chromosomal locations of genes that influence these phenotypes. For DNA markers that give suggestive evidence of linkage, analyses will be expanded to include additional markers in these regions, utilizing multipoint methods. To improve genetic models, strengthen evidence for linkage, and reduce the number of false positives, gxE interactions and pleiotropic and epistatic effects of major genes will be quantified. Oligogenic analysis will strengthen linkage signals and further reduce false positives, and disequilibrium analysis will improve localization of genes influencing quantitative CVD risk factors. Genes localized in Project 1 will guide the selection of candidate genes for molecular studies in Project 2. These analyses will set the stage for future efforts to identify the major genes and understand their functions.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
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
Chittoor, Geetha; Kent Jr, Jack W; Almeida, Marcio et al. (2016) GWAS and transcriptional analysis prioritize ITPR1 and CNTN4 for a serum uric acid 3p26 QTL in Mexican Americans. BMC Genomics 17:276
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

Showing the most recent 10 out of 258 publications