The concept of the testicular dysgenesis syndrome (TDS) suggests that male infertility, cryptorchidism, hypospadias, impaired spermatogenesis and testicular germ cell cancer often have a common origin. In a systems biology framework, by combining a genome-wide association study with gene expression and mouse knock-out data to study the genetic components that predispose to TDS, we identified genes involved in TGFβ signaling that were significant across the TDS phenotypes. Our findings are particularly important because TDS is steadily increasing in western countries, thereby also increasing the need of assisted reproduction. We expect this work to be the basis of new functional studies and genomic fine mapping of the key loci identified. (By Dr Ramneek Gupta, http://jmg.bmj.com/content/early/2011/12/02/jmedgenet-2011-100174.abstract?papetoc )