Precision Medicine

Power in Numbers in an International Collaboration 

Pulmonary arterial hypertension (PAH), a disease characterized by elevated pulmonary artery pressure, is a serious and progressive condition that most often affects children with underlying cardiac or lung disease, and that can result in right ventricular failure. Genetic studies over the last few years have revealed that mutations in the gene encoding a specific bone protein receptor (BMPR2) are responsible for about three quarters of cases of pulmonary arterial hypertension (PAH) that occurs in families, and for approximately 20 percent of apparently sporadic cases of idiopathic PAH. Although environmental factors may account for some cases of idiopathic PAH, it seems likely that additional novel rare genetic variations underlie a significant proportion of cases. Moreover, common or rare genetic variations may influence the penetrance of the known genes and the clinical course/response to therapy. Clinical geneticist Wendy Chung, MD, PhD is working with participants from North America and Europe in the International Consortium for Genetic Studies in PAH. With a pool of thousands of samples from patients with idiopathic and heritable PAH, the collaborators should have the statistical power to discover the complete genetic architecture of PAH, and address the major questions regarding the role of genetic variation in disease penetrance, phenotype, and the clinical course of disease.