Al‐Naamani N, Krowka MJ, Forde KA, et al. - Researchers conducted a multicenter case‐control study to ascertain if genetic variants and metabolites in the estrogen signaling pathway are correlated with portopulmonary hypertension (POPH). POPH patients had mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dyn‐sec/cm−5, and pulmonary artery wedge pressure ≤15 mm Hg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure <40 mm Hg, and normal RV function by echocardiography. Participants in the study were 37 patients with POPH and 290 controls. The risk allele A in rs7175922 (CYP19A1) was significantly linked to higher levels of estradiol and an increased risk of POPH while other SNPs were not. POPH was associated with lower urinary 2‐hydroxyestrogen/16‐α‐hydroxyestrone, lower plasma levels of dehydroepiandrosterone‐sulfate, and higher plasma levels of 16‐α‐hydroxyestradiol. Findings suggested an association of genetic variation in aromatase and changes in estrogen metabolites with POPH.