Venous Thromboembolism Polygenic Risk Score Associates With Pulmonary Hypertension in the UKBiobank

摘要

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) driven by incomplete resolution of pulmonary embolism and adverse vascular remodeling.1 A recent review of epidemiologic data suggests that CTEPH is relatively rare, with an incidence in the United States and Europe of 3 to 5 cases/100 000 individuals per year and a calculated 4 to 7 cases per million.2 However, CTEPH is likely underdiagnosed due to the subtlety of symptoms early in the disease, as well as its development in individuals with no known history of pulmonary embolism; a study utilizing estimated incidence of pulmonary embolism and resultant CTEPH, and data from pulmonary endarterec-tomies in the United States and Europe, indicates only 1 4% of cases are diagnosed.2 The familial enrichment of CTEPH cases and heightened venous thromboembolism (VTE) risk among relatives of individuals with CTEPH implies a heritable component.3 Large-scale biobanks have enabled interrogation of common genetic variants that increase disease risk, including those which strongly associated with VTE.4 Here, we hypothesized that genetic determinants of VTE might also promote downstream sequelae, such as PH, in the general population.