The frequency of the COMT rs4680 “GA” and “AA” genotypes was modestly higher in PD patients with depression than those without depression (42.2% vs. 25.7%, P = 0.01, Supplementary Table 2), and the presence of the “A” allele significantly increased the risk of depression in patients with PD ([OR] = 1.89, 95% CI = 1.15–3.10, 1.89, P = 0.01). Here, COMT is linked to major depressive disorder.