Considering direct and indirect effects of estrogen on follicle development, maturation, and ovulation mediated by ERα and ERβ, polymorphisms of ESR1 and/or ESR2 would be expected to be associated with persistent anovulation in PCOS and an ocean of studies focused on genetic variations in ESR1 and ESR2 with pathological dysfunction of ovulation. Here, ESR1 is linked to polycystic ovary syndrome.