In contrast to the candidate gene approach, the GWAS approach is largely an exploratory approach without any prior knowledge or hypothesis about the genes or underlying biological mechanisms; it involves scanning the entire genome for possible associations using hundreds of thousands of markers providing a dense coverage of every chromosome. The obvious benefit of this approach is that it provides an exhaustive coverage of the whole genome. However, it also has some caveats. First, as in linkage studies, markers showing an association signal may not necessarily be causal variants, and the latter still need to be determined by fine mapping and sequencing of the region. Second, due to a massive multiple testing problem inherent to this approach and, consequently, the need to adjust the significance threshold, very large samples (of the order of thousands or even tens of thousands) are necessary to conduct a GWAS study with sufficient statistical power. In GWAS studies of psychopathology phenotypes conducted to date, this problem is further exacerbated by small effect sizes necessitating further increase in sample size in order to detect a significant
