Child μ-Opioid Receptor Gene Variant Influences Parent–Child Relations

Author(s): William E Copeland, Hui Sun, E Jane Costello, Adrian Angold, Markus A Heilig and Christina S Barr


Variation in the μ-opioid receptor gene has been associated with early social behavior in mice and rhesus macaques. The current study tested whether the functional OPRM1 A118G predicted various indices of social relations in children. The sample included 226 subjects of self-reported European ancestry (44% female; mean age 13.6, SD=2.2) who were part of a larger representative study of children aged 9-17 years in rural North Carolina. Multiple aspects of recent (past 3 months) parent-child relationship were assessed using the Child and Adolescent Psychiatric Assessment. Parent problems were coded based upon a lifetime history of mental health problems, substance abuse, or criminality. Child genotype interacted with parent behavior such that there were no genotype differences for those with low levels of parent problems; however, when a history of parent problems was reported, the G allele carriers had more enjoyment of parent-child interactions (mean ratio (MR)=3.5, 95% CI=1.6, 8.0) and fewer arguments (MR=3.1, 95% CI=1.1, 8.9). These findings suggest a role for the OPRM1 gene in the genetic architecture of social relations in humans. In summary, a variant in the μ-opioid receptor gene (118G) was associated with improved parent-child relations, but only in the context of a significant disruption in parental functioning.


by William Copeland
The primary finding of the manuscript was the link between the OPRM1 A118G SNP and social behavior in children. In this study the focus was on the relationship between the child and their primary caregiver. The G allele proved protective to this relationship in the face of parental unavailability. When the parent had no impediment to providing the child optimal care, there was no effect of the genetic marker.  As such, this allele may provide a genetic basis for "resilience" to impaired attachment in the face of a significant disruption in the parent's functioning. 

There have been numerous candidate gene studies in neuropsychiatry over the years and many significant effects have failed to be replicated. We believe that is unlikely to be the case here for a number of reasons. First, this study converges with results from an OPRM1 knock-out mouse study and our previous work on the rhOPRM1 C77G SNP in macaques. In each case a variation in the mu-opioid receptor gene affected parent-child relations and in each case, this effect was pronounced in the context of parent-child separation. Second, this finding converges with accumulating evidence that the opioid-modulated mesocorticolimbic dopaminergic pathway activity accounts for the rewarding aspects of social interactions. Finally, we focused on narrowly-defined quantitative phenotypes and tested multiple, independent indices of parent-child interaction phenotypes.

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