This is well illustrated by the recent identification of the association of a variant of the gene for the ER-α with hypospadias and cryptorchidism in Japanese cohorts (Watanabe et al. 2007; Yoshida et al. 2005) that has now been found to be associated with a decreased incidence of hypospadias in a European cohort (Galan et al. 2007). The gene discussed is ESR1; the disease is cryptorchidism.