Benefits and pitfalls encountered in psychiatric genetic association studies

The basic methodology utilized in each step of a typical psychiatric genetic association study is reviewed and their potential benefits and pitfalls are discussed with particular emphasis on the selection of clinical phenotype.

Abstract

The genetic association strategy is currently being applied to a number of psychiatric phenotypes including disease vulnerability, personality variation and clinical response to psychotropic drugs. Association studies offer the prospect of identification of the specific alleles that confer significant effects on clinical phenotype. However, it should be noted that this strategy has additional advantages as well as unique drawbacks. In this paper, we review the basic methodology utilized in each step of a typical psychiatric genetic association study and discuss their potential benefits and pitfalls with particular emphasis on the selection of clinical phenotype, the identification of a candidate gene, the selection of a candidate variant, clinical data set design, and the statistical analysis of association data. With appropriate design and execution, it is hoped that the association strategy will prove to be as successful in psychiatry as it has proven to be in other branches of medicine.