The functional candidate gene approach is restricted by our limited knowledge of the biological pathways underlying the etiology of schizophrenia. However, one of the most common and widely accepted hypotheses is the “dopamine hypothesis.” This proposes that a dysfunction in the dopaminergic neurotransmitter system, which leads to a reduced dopamine concentration in cortical regions and to an excess of dopamine in striatal areas of the brain, is involved in the pathogenesis of schizophrenia (for review see Howes and Kapur, 2009). Genes involved in dopaminergic neurotransmission such as the dopamine transporter 1 (DAT1), dopamine receptor 1–5 (DRD1–5), and catechol-O-methyltransferase (COMT) are therefore major candidates for genetic association studies. Variants in these genes have been found to be associated with schizophrenia in independent studies (e.g. Sivagnanasundaram et al., 2000; Shifman et al., 2002; Jönsson et al., 2003; Staddon et al., 2005; Shi et al., 2008; Talkowski et al., 2008), although none of these findings have been unequivocally accepted since there has been insufficient evidence across studies (e.g. Jönsson et al., 2001, 2004; Georgieva et al., 2002; Serretti et al., 2004; Okochi et al., 2009).
