Dr. O’Donnell research is broadly focused on the epidemiology of complex cardiovascular disease (CVD), the leading cause of death and disability in men and women. More specifically, Dr. O’Donnell has focused on the genetic and genomic epidemiology of clinical and subclinical forms of atherosclerosis, ventricular hypertrophy and thrombosis. A large genome-wide association study is being directed by Dr. O’Donnell in a large, well-phenotyped prospective study of multigenerational families drawn from a general population (the NHLBI’s Framingham Heart Study SHARe Project). Heritable clinical and intermediate CVD phenotypes of interest include premature onset CVD, circulating biomarkers (e.g., hemostasis and thrombosis factors) and subclinical atherosclerosis detected by high resolution cardiovascular imaging (e.g., coronary artery calcium by cardiac computed tomography and aortic plaque detected by cardiovascular magnetic resonance imaging). Using both genome-wide linkage and newer association methods, Dr. O’Donnell’s group has identified a number of single nucleotide polymorphisms and haplotypes with evidence for causal associations with atherosclerosis, hypertrophy and thrombosis. The long-term goal for this marriage of genomic science with well-designed studies of human populations is to better understand the etiology of CVD and to discover new targets for preventing, pre-empting and treating CVD.