Polymorphisms in sex steroid receptors: From gene sequence to behavior.

Sex steroid receptors have received much interest as potential mediators of human behaviors and mental disorders. Candidate gene association studies have identified about 50 genetic variants of androgen and estrogen receptors that correlate with human behavioral phenotypes. Because most of these polymorphisms lie outside coding regions, discerning their effect on receptor function is not straightforward. Thus, although discoveries of associations improve our ability to predict risk, they have not greatly advanced our understanding of underlying mechanisms. This article is intended to serve as a starting point for psychologists and other behavioral biologists to consider potential mechanisms. Here, I review associations between polymorphisms in sex steroid receptors and human behavioral phenotypes. I then consider ways in which genetic variation can affect processes such as mRNA transcription, splicing, and stability. Finally, I suggest ways that hypotheses about mechanism can be tested, for example using in vitro assays and/or animal models.