The principal findings of the present genetic study using WES data are that five variants in the PDE4A, FDX1L, and MYO15B genes are associated with increased risk of depressive disorder in women, that depressive patients homozygous for these variants are more likely to experience severe depressive symptoms, and that a higher genetic burden is required for men to develop depressive disorder, particularly of protein-truncating and deleterious variants, which may contribute to the higher resilience of male individuals against depressive disorder. Here, MYO15B is linked to depressive disorder.