Significant sexual dimorphism in prevalence, age of onset, severity, or genetic risk is observed for most common human diseases. Elucidating the underlying mechanisms for these observations remains challenging, but represents an important area for future research. Because it is unlikely that sexually dimorphic traits are due to differences in the structure of genes in males and females (with the possible exception of genes on the Y chromosome), the importance of the regulatory genome in this context becomes central to understanding mechanism. Standing variation in regulatory elements that contribute to sexually dimorphic traits could result in sex-specific gene–environment interactions. In addition, sexually dimorphic developmental processes, such as sex-specific changes in gene regulation with age85, can result in shifting differences in disease susceptibility between the sexes, for example, as has been observed for asthma (Figure 3).
