Besides, TSH also modulates endothelial function via TH receptor-α1 and TH receptor-β pathways,[38] impairing vascular smooth muscle relaxation and nitric oxide availability, thereby increasing arterial stiffness and systemic vascular resistance.[39] Meanwhile, the MR-derived causal association between hypothyroidism and HTN (OR = 1.10, P = .024) may be partly mediated by renin-angiotensin-aldosterone system dysfunction. The gene discussed is REN; the disease is hypertensive disorder.