and there is no main effect of naltrexone, one cannot effectively discriminate between alternative interpretations: one being that there is no effect of OPRM1 variation on naltrexone response and the second being that the study failed to identify a naltrexone effect because of extraneous factors (e.g., study population, powerful ancillary treatment, high dropout rate, etc.). Yet, another plausible explanation for the mixed findings is that the effect size of this pharmacogenetic interaction is small. There is increasing recognition in behavioral genetics that psychiatric disorders may be due to multiple genes of small effect size (Plomin et al., 2009). Applying a similar polygenic framework to pharmacogenetic studies would suggest a relatively small effect size for this particular pharmacogenetic finding, which in turn can account for the mixed findings. In fact, a recent review of genetics of alcoholism argued that there may be a modest pharmacogenetic effect of the Asp40 allele on response to naltrexone and that large prospective studies are needed to more accurately estimate the effect size of this interaction (Gelernter and Kranzler, 2009).
