Biochemical genetic differences in vulnerability to drug effects: is statistically significant always physiologically important and vice versa?

Abstract

The goal of biochemical genetic experiments, which are designed to better understand vulnerability to drug effects, is to determine variation in biochemical traits which can account for variation in behavioral and physiological effects of drugs. Biochemical genetic experiments commonly span several distinct scientific disciplines and many different methodologies, both behavioral and biochemical. In most cases, biochemical genetic experiments involve at least three different levels of analysis, including sophisticated mathematical models of genetic inheritance, many behavioral paradigms used to assess various drug-related phenotypes, and a variety of biochemical methodologies used to determine biochemical correlates. Both the multidisciplinary nature of this scientific endeavor and the traditional uses of the scientific methods which are now being applied to pharmacogenetic experiments necessitate careful consideration of many often conflicting theoretical perspectives in the process of interpretation of experimental results. Several scientific considerations are discussed which emphasize the presentation of the results of pharmacogenetic studies within the context of expectations concerning genetic variance as well as traditional uses and assumptions related to methodology.