In recent years, the combination of advances in our understanding of human genomic variation (e.g., Human Genome Project; HapMap Project; 1,000 Genomes Project) and cost-effective genotyping techniques haveled to extraordinary growth in molecular genetic studies of depression and other “complex” psychiatric phenotypes. These studies typically examine whether specific alleles (e.g., alternative forms of DNA sequence at a specific locus) or genotypes (e.g., the combination of alleles at a given locus) are associated with the phenotype of interest. Until recently, genetic studies of depression focused largely on candidate genes, or genes hypothesized to be implicated in the neurobiology of depression. Some of the most commonly studied candidate genes have been those regulating serotonin (5-HT) and dopamine (DA) neurotransmission, given the suspected involvement of these neurotransmitters in the pathophysiology of depression and the fact that these are targets of antidepressant drugs.25-27 Unfortunately, most candidate gene studies have been underpowered and replication of findings has been rare. More recently, the availability of DNA microarrays have enabled genomewide association studies (GWAS) that do not rely on prior hypotheses. The GWAS approach allows for the
