Candidate gene studies focus on genetic polymorphisms selected by their biological relevance to the studied phenotype. Usually, these are functional polymorphisms, i.e. their selection is based on the evidence that they produce functional effects at the molecular and cellular level such as changes in gene expression, enzyme activity, or receptor characteristics. Most of the association studies involving psychophysiology-relevant phenotypes were conducted using this approach. The Candidate gene approach has obvious strengths: it is hypothesis driven, utilizes genetic variants that are likely to be causal variants, and therefore has a strong potential to provide a mechanistic explanation for the observed association. Finally, it usually involves a limited number of statistical tests, thus mitigating the multiple comparisons problem. Consequently, this analysis does not require very large samples, which is an important consideration for phenotypes that are difficult and costly to measure, such as psychophysiological or neuroimaging phenotypes. However, in recent years, this approach has drawn much criticism for its inherently restrictive nature, i.e. limiting the search for genes involved in the determination of complex phenotype to a handful of apriori selected variants
