There are important limitations to our analysis. First, we have little reliable data about the genetic basis of complex traits in general and psychiatric endophenotypes in particular. Assumptions about the genetic architecture of complex traits depend so far largely on negative findings: our inability to detect robust linkage and association signals is due to lack of power and we have not sufficiently appreciated the genetic complexity. It is possible that, with the completion of the first whole genome association studies when estimates of effect size across the genome are available, a different picture will emerge. A second important limitation is that our review has concentrated on the effect of COMT on endophenotypes. Unfortunately there are no other examples where sufficient data have accumulated to be included in meta-analyses. Again, the availability of additional data might alter our results.
