: This Program Project supports the San Antonio Family Heart Study (SAFHS), the first comprehension genetic epidemiological study of atherosclerosis and its correlates in Mexican Americans. It's long-term goal is to detect, characterize, map, and identify new polymorphic genes that influence variation in susceptibility to cardiovascular disease (CVD). More than 1,400 members of 41 extended Mexican American families were recruited without regard to disease status and examined during the first grant period (SAFHS1), and 859 family members were recalled during the current grant period(SAFHS2). Genotyping of all family members for 414 markers in a 10 centimorgan map will be complete by the end of the current grant period. Data from nearly 500 members of 10 large families (Pedigree Set A) have been used to successfully detect and map quantitative trait loci (QTLs) influencing leptin, fat mass, BMI, insulin, 2 hour glucose, LDL-3-HDL-C, HDL2a unesterified cholesterol, several measures of median HDL particle size, P-selectin, and VCAM-1. For regions with the strongest evidence for linkage, additional markers are being typed for use in finer scale mapping strategies. With the completion of the genome scan for the remaining family members, SAFHS investigators are poised to exploit the valuable resource created during the past 10 years. For two of the most promising findings, an effort will be launched to identify the functional polymorphisms accounting for linkage signals for leptin and HDL2a in chromosomal regions with strong positional candidates genes (POMC and LIPC, respectively). QTLs for phenotypes for which strong signals have not yet been detected will mapped and chacterized in the larger data set. The most promising leads will be pursued by refining linkage signals, characterizing interactions and pleiotropy, assessing associations with candidate genes polymorphisms, and seeking to identify the QTS. Novel phenotypes of the adipo-insular axis and phenotypes related to inflammation and oxidative stress also will be targeted. These new phenotypes, as well as glucose, insulin, leptin, total and HDL cholesterol, and lipoprotein size phenotypes, will be assessed in a recall of 950 family members. Taking advantage of 5- and 10-year longitudinal data, SAFHS investigators will seek to map genes that influence age-related changes in CVD risk factors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL045522-15
Application #
7076158
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Rabadan-Diehl, Cristina
Project Start
1991-09-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2008-05-31
Support Year
15
Fiscal Year
2006
Total Cost
$2,494,758
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
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