Serotonergic antidepressant use was significantly associated with PDE-5 inhibitor use (OR = 3.6 [2.8, 4.8], p < 0.001), and this association remained significant after adjusting for age, SES, BMI, depression, and anxiety (OR = 3.2 [2.3, 4.4], p < 0.001). This evidence concerns the gene PDE5A and major depressive disorder.