It is now thought that the genetic architecture of mental disorder is very complex, and may be difficult to resolve using standard GWA approaches (Manolio, et al., 2009; The Psychiatric GWAS Consortium Steering Committee, 2009). In particular, Keller and Miller (2006) argue, based on evolutionary genetic theory and empirical evidence, that mental disorder is likely to be due to the aggregate effect of many mildly harmful rare mutations, impossible to detect with standard GWA studies. However, using similar evolutionary genetic theory, Penke, Dennison and Miller (2007) argue that personality traits are likely to be under balancing selection, and therefore influenced by a limited number of common genetic variants of medium effect. If this is true, personality may be an ideal psychological trait to attack with the GWA approach.
