Statistical analyses revealed that rare predicted deleterious variants in seven genes were significantly associated with IPAH, including three established PAH risk genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17 and KDR) and two new candidate genes (FBLN2 and PDGFD). This evidence concerns the gene TBX4 and idiopathic pulmonary arterial hypertension.