The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.

Obesity is globally prevalent and highly heritable, but the underlying genetic factors remain largely elusive. To identify genetic loci for obesity-susceptibility, we examined associations between body mass index (BMI) and ~2.8 million SNPs in up to 123,865 individuals, with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity-susceptibility loci and identified 18 new loci associated with BMI (P<5×10−8), one of which includes a copy number variant near GPRC5B. Some loci (MC4R, POMC, SH2B1, BDNF) map near key hypothalamic regulators of energy balance, and one is near GIPR, an incretin receptor. Furthermore, genes in other newly-associated loci may provide novel insights into human body weight regulation.

The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 cases and 64,762 controls of European descent, followed by genotyping of top association signals in 60,738 additional individuals. This genomic analysis identified 13 novel loci harboring one or more SNPs that were associated with CAD at P<5×10−8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 novel loci displayed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6 to 17 percent increase in the risk of CAD per allele. Notably, only three of the novel loci displayed significant association with traditional CAD risk factors, while the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the novel CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.