Background The capacity to control or regulate one’s emotions, cognitions and behavior is central to competent functioning, with limitations in these abilities associated with developmental problems. Parenting appears to influence such self-regulation. Here the differential-susceptibility hypothesis is tested that the more putative ‘plasticity alleles’ adolescents carry, the more positively and negatively influenced they will be by, respectively, supportive and unsupportive parenting. Methods One thousand, five hundred and eighty-six (1586) adolescents (n = 754 males; n = 832 females) enrolled in the American Add Health project were scored in terms of how many of 5 putative ‘plasticity alleles’ they carried – the 10R allele of DAT1, the A1 allele of DRD2, the 7R allele of DRD4, the short allele of 5HTTLPR, and the 2R/3R alleles of MAOA. Then the effect of the resultant index (ranging from 0 to 5) of cumulative-genetic plasticity in moderating effects of parenting on adolescent self-regulation was evaluated. Results Consistent with differential susceptibility, the more plasticity alleles males (but not females) carried, the more and less self-regulation they manifested under, respectively, supportive and unsupportive parenting conditions. Conclusion Adolescent males appear to vary for genetic reasons in their susceptibility to parenting vis-à-vis self-regulation, perhaps due to epistatic and/or epigenetic processes. G×E research may benefit from compositing candidate genes. To afford comparative evaluation of differential-susceptibility vs. diathesis-stress models of environmental action, future G×E work should focus on positive as well as negative environmental conditions and developmental outcomes.

Gottfredson and Hirschi's general theory of crime (1990) has generated an abundance of research testing the proposition that low self-control is the main cause of crime and analogous behaviors. Less empirical work, however, has examined the factors that give rise to low self-control. Gottfredson and Hirschi suggest that parents are the sole contributors for either fostering or thwarting low self-control in their children, explicitly discounting the possibility that genetics may play a key role. Yet genetic research has shown that ADHD and other deficits in the frontostriatal system are highly heritable. Our research thus tests whether "parents matter" in creating low self-control once genetic influences are taken into account. Using a sample of twin children we find that parenting measures have a weak and inconsistent effect. We address the conceptual and methodological issues associated with the failure to address genetic influences in parenting studies.More than a decade ago, Gottfredson and Hirschi (1990) set forth a general theory of crime that assigned low self-control as the causal factor in the etiology of crime and numerous analogous behaviors. Since that * We would like to thank the editor for his commitment to scholarly discourse.

The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.