We contend that this “biological validation” argument is weak, subjective, prone to incorrect decisions, and liable to divert downstream research efforts by emphasizing the wrong targets. First, as documented in this paper, biology-driven candidate gene studies have not been particularly useful. Second, because we understand so little of the pathogenesis of schizophrenia, we have no biological gold standards or first principles. Put simply, there is neither a biology that we can demand of a ‘”true” associated gene nor a biology that is inconsistent with a “false” gene. Third, how then can we assess the validity of the biological connection being made? For genetics to achieve its goal of providing secure entry points into the biology of schizophrenia, findings must stand on their own merits without reference to other biological hypotheses or data. To do otherwise inevitably leads to circular reasoning (i.e., speculative biological supported by weak genetics supported by biological speculation).
