We work on large scale genomic studies within a variety of international consortia to unravel the genetic determinants of cardiovascular disease and its risk factors, with a special emphasis on hemostatic factors. We are most active within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the Trans-Omics for Precision Medicine (TOPMed) program, but also participate in other consortia. We are particularly interested in translational approaches such as Mendelian randomization and genetic risk prediction, and we welcome collaborations with wet lab teams to unravel the biology underlying the discovered loci.
Uncovering the genetics of hemostasis and thrombosis
Our lab has contributed to and led multiple studies in the CHARGE consortium Hemostasis Working Group that have resulting in the discovery of genetic loci associated with circulating levels of coagulation factor proteins, including fibrinogen, Factor VII, Factor VIII, von Willebrand Factor, and more. We have been able to leverage the results from these genetic studies to perform Mendelian randomization analyses, identifying potential causal effects of hemostatic factors on thrombotic outcomes. Specifically, we provided evidence for a causal effect of Factor VII levels on ischemic stroke, as well as for a causal effect of levels of von Willebrand Factor and Factor VIII on ischemic stroke, venous thromboembolism, coronary artery disease, and peripheral artery disease. We also showed that gamma prime fibrinogen may have a protective causal effect on venous thromboembolism, cardioembolic stroke, and large artery stroke.
Polygenic risk scores for prevention of cardiometabolic diseases
We have sought to examine the role polygenic risk scores can play in the primary prevention of diseases such as coronary artery disease and type 2 diabetes. To date, our focus has been on the impact of these scores on lifetime risk of disease and years lived free of disease. Specifically, we showed that individuals with high polygenic risk score could offset their genetic extra risk of type 2 diabetes with a healthy BMI. Similarly, we showed that individuals with high polygenic risk score could offset their extra risk of coronary artery disease with a healthy lifestyle, as measured by the Life’s Simple 7 score. Individuals with a high polygenic risk score but an ideal Life’s Simple 7 score lived an additional 20 years free of coronary artery disease compared to those with the same polygenic risk score but poor Life’s Simple 7 score.