 My name is Roxana Donis-Jew and I'm excited to share with you our recent work on finding a population-specific single nucleotide polymorphism that conferred an increased risk of phenostromboembolism in African Americans. Our paper is published in Molecular Genetics and Genomic Medicine. There are 300,000 to 900,000 cases of deep vein thrombosis and pulmonary embolism in the United States alone each year. What exactly are deep vein thrombosis, also known as DVTs, and pulmonary embolisms, also known as PES? In a deep vein thrombosis, a clot forms in a vein, usually one of the deeper veins of the leg. This can cause significant pain and swelling in the local area. This clot can also become dislodged and travel back to the right side of the heart and then get pumped into the vasculature of the lungs. If the clot is big enough, it can impede blood flow, keeping blood from being oxygenated. A big enough PE can result in death. In individuals of African American descent, the incidence of this disease is 30 to 60% higher than in individuals of European descent. Yet, most of what we know about genetic risk factors for DVTs and PES have been studied in individuals of European descent. So as I mentioned before, we don't know much about genetic risk factors for DVT-PE in African American descent individuals. That's why when we were doing a study looking at genetic risk factors for the dosing of the anticoagulant warfarin, we became very excited when we made a serendipitous discovery. During a quality control step where I was making sure that none of the individuals were related to one another in the study, we found that three individuals had high genetic similarity. This genetic similarity seemed to indicate that they were a mom with two daughters. It's a little bit strange for three people in the same family to all be on warfarin. So I went back to look at what was their indication for being on the drug. I found that they all had a history of multiple DVTs and PES. I went back to our clinical collaborators to say, see if we could find out more about this family. This pedigree represents the history of thromboembolism that we see in the family. The individuals labeled one, two, and three were all exome sequenced for a previous project. We didn't have any access to any other family members, but based on the exome data of three individuals, we were able to find a candidate variant, a mutation in protein S. After we found our candidate mutation in protein S, we were able to get permission to mine the clinical data of these three individuals. The clinical data revealed that all three family members had a deficiency in free protein S. This clinical data supported what we had found genetically. Once we had both genetic and clinical evidence of a protein S mutation, possibly causing hereditary thromboembolism in our family, we had another important question. Does this mutation have an effect in the population? We created a multicenter cohort of 306 African American cases with either DVT or PE and 370 African American controls. Using this data, we found that the protein S mutation was significantly enriched in the DVT-PE group with an odds ratio of 4.6. We found a mutation in protein S, an anti-coagulant protein. Previously, mutations in this protein have led to hereditary deep vein thrombosis and pulmonary embolism in European descent families. In many of those cases, those mutations were private to that family and quite rare. In contrast, the mutation we found has about a 1% frequency in African descent populations. We presented here a population-specific genetic risk factor for DVT-PE in individuals of African descent. We hope there are many future studies looking at additional genetic risk factors for this disease in this understudied population. To find out more about our study, read our paper.