In this section we discuss developments in two areas, first brain imaging and then gene by environment interactions (G × E for short). For many years psychiatric geneticists have had difficulties establishing robust associations between disease phenotype and allelic variant, leading some to argue that it would be better to work with phenotypes where the genetic architecture consists of loci of larger effect. Proponents of this uncontroversial proposition have suggested that neuroimaging phenotypes have the requisite property: that genetic effects on brain structural and functional variation are necessarily larger. The claim is based on the assumption that some phenotypes (often called endophenotypes) are biologically closer to the site of genetic variation (measures of mRNA would be an extreme example) and therefore the impact of genetic variation must be larger. Thus one study of just twenty-eight subjects reported an association between variation in amygdala activation and variation in a length polymorphism of the serotonin transporter gene (5-HTTLPR) [15]. The ‘short’ allele at this frequently typed polymorphism has a frequency of about 30% in European populations, and is thus a typical common
