Benefits and pitfalls encountered in psychiatric genetic association studies

The genetic association strategy is currently being applied to a number of psychiatric phenotypes including disease vulnerability, personality variati on and clinical response to psychotropic drugs. Association studies offer t he prospect of identification of the specific alleles that confer significa nt effects on clinical phenotype. However, if should be noted that this str ategy has additional advantages as well as unique drawbacks. In this paper, we review the basic methodology utilized in each step of a typical psychia tric genetic association study and discuss their potential benefits and pit falls with particular emphasis on the selection of clinical phenotype, the identification of a candidate gene, the selection of a candidate variant, c linical data set design, and the statistical analysis of association data, With appropriate design and execution, it is hoped that the association str ategy will prove to be as successful in psychiatry as it has proven to be i n other branches of medicine. Biol Psychiatry 1999;45: 544-550 (C) 1999 Soc iety of Biological Psychiatry.