SMAD4 and pulmonary arterial hypertension: We screened for rare, predicted deleterious variants (allele frequency < 0.01% and likely gene damaging (LGD) or missense with REVEL score > 0.5 (D-Mis), see the “Methods” section) in 11 established PAH risk genes [38–41]: ACVRL1, BMPR1A, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, KCNK3, SMAD4, SMAD9, and TBX4 by targeted capture/sequencing, multiple ligation-dependent probe amplification (MLPA) (to evaluate deletions/duplications in BMPR2, ACVRL1, and ENG only), and exome sequencing.