Some of these suggestive associations included major depressive disorder and PTEN, a tumor suppressor gene (burden of non-synonymous variants: OR = 9.15, Firth’s p-value = 1.5 × 10–4); substance addiction and disorders and KCNQ1, which encodes a potassium channel protein (burden of damaging missense variants: OR = 14.63, p-value = 2.4 × 10–4), and depression and CACNA1S, a calcium channel gene (burden of all rare variants: OR = 1.50, p-value = 5.8 × 10–4; Table 1). This evidence concerns the gene KCNA3 and major depressive disorder.