The Kruskal-Wallis test revealed a significant difference between the ESS categories among participants with prior epistaxis-related treatment (5.2), anemia (5.6), pulmonary hypertension (6.1), shortness of breath (5.5), hemoptysis (5.8), headache (5.4) (all p < 0.001); lung AVMs (4.6), SMAD4 genetic mutation (5.2), heart failure (5.9) (all p = 0.001); and seizures (6.2) (p = 0.004) (Supplement 2: eTable 3). This evidence concerns the gene SMAD4 and pulmonary arterial hypertension.