Dr. Rich’s research is centered on understanding the genetic epidemiology of complex human disease, including the genes contributing to type 1 diabetes and its complications, atherosclerosis, stroke and their intermediate phenotypes (risk factors). These studies range from interrogating the effects of subclinical markers of disease risk, to gene mapping, gene discovery, and understanding the functional significance of the disease-associated variants. A long-term focus of research is the genetic basis of type 1 diabetes, with establishment of the Type 1 Diabetes Genetics Consortium (T1DGC), in which over 40 loci have been mapped and T1D “causal genes” have been identified. Examination of variants and functional significance is a key step in designing targeted interventions. In the realm of atherosclerosis and risk factors, the primary study population is the Multi-Ethnic Study of Atherosclerosis (MESA), a collection of ~6,800 adults (aged 45+) without evidence of clinical disease. These participants (Caucasian, African-American, Hispanic-American, Chinese-American) have extensive imaging, biomarker and clinical longitudinal data, as well as DNA for genetic studies. MESA has been the subject of genome-wide association and linkage scans, evaluation by the MetaboChip (a custom high-density genotyping array), and contributed samples to the NHLBI Exome Sequencing Project (ESP). All MESA participants have been genotyped by the ExomeChip in order to assess the role of rare variants in atherosclerosis risk. A primary goal of these research efforts is to identify novel genes and pathways that can serve as predictors of risk, identify those at highest risk of disease and, therefore, amenable to intervention, and to develop models of disease through manipulation of these genes and thus identify potential therapeutic targets.