Several limitations should be acknowledged. The sample size for the postmortem analyses is relatively small. Detecting the functional effects of genetic variation in postmortem tissue would benefit greatly from larger sample sizes. Because the results were consistent across the different studies in this article, we have confidence in these findings, although a larger sample size would be useful for providing a definitive test of the association between rs2023239 and CB1 receptor levels. Larger sample sizes in the context of the neuroimaging, behavioral, and clinical studies would also be helpful for testing the additive effects of genetic markers (eg, the DRD4 variable number of tandem repeats polymorphism33,34,49 and the μ-opioid receptor gene [OPRM1] A/G SNP50,51) that have also been linked to these phenotypes. Another commonly cited limitation is population stratification. Although it is always possible that the results may be confounded by population stratification or other third variables,52 it is highly unlikely in the present study because the participants in each of the data sets were predominantly white (approximately 95%) and the findings were consistent across multiple studies and levels of
