of the association may also be related to the differences in the sample ascertainment. In both CEDAR/SADS and COGA samples, the affected individuals, ascertained clinically, have a relatively severe DUD, frequently related to polysubstance abuse, whereas in the population-based Virginia sample, the drug abuse is less severe. It is conceivable that recreational drug use that does not involve/reach clinical strength drug abuse/dependence may be itself an attribute of affiliative behavior and thus related to the prosocial function of the AVPR1A, whereas the other allele may be associated with elevated antisociality, a frequent attribute of and precursor to a clinical DUD that requires stepping over a higher liability threshold. The potential explanations are probably not restricted to these possibilities and are not mutually exclusive. Regardless of its source, however, the flip-flop suggests caution in assigning risk or protection modalities to allelic effects in variation in complex traits.
