Archive for the ‘GABRA2’ Category

Teenagers are (in)famous for their hysterics.  They are biologically mature, but society and their parents don’t allow them the freedom they desire.  Toss in a steady diet of advertisement-laced TV … often for alcohol (an average of 301/year in 2007 – up from 216 in 2001), and you’ve got an enduring (not endearing) epic struggle.

Now toss the human genome … into the drowsy parents-watching-teenagers-watching beer ads on TV (until drowsy parents fall asleep and the real fun begins).  Will it lead to a night of harmless fun? or a lifetime struggle full of rehab and alcohol addiction?

The research article, “Role of GABRA2 in Trajectories of Externalizing Behavior Across Development and Evidence of Moderation by Parental Monitoring” suggests that some of the genetic risk for alcoholism is foreshadowed in, or somewhat overlapping with, the externalizing behaviors of teenagers.  Furthermore, the role of parental oversight can interact with, and reduce this genetic risk.

Here we present analyses aimed at delineating the pathways of risk associated with GABRA2 OMIM 137140. This gene was originally associated with adult alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) project.13 The association with adult alcohol dependence has been replicated in several independent samples.1417 Subsequent analyses of GABRA2 in the COGA sample also yielded evidence of association with other forms of drug dependence,18,19 antisocial personality disorder,20 and childhood conduct disorder,19 leading to the hypothesis that GABRA2 may be involved in the predisposition to alcohol dependence through general externalizing pathways.21

Importantly, parental monitoring has been shown to moderate the importance of genetic effects on substance use across adolescence.29,30 In a population-based sample of twins aged 14 and 17 years, as parental monitoring increased, genetic effects on substance use significantly decreased.30

Using data on externalizing behavior as reported at 9 time points between ages 12 and 22 years, we used person-oriented latent class analysis to identify 2 classes of trajectories of externalizing behavior; most of the sample (83%) showed a decrease in externalizing behavior from early adolescence to adulthood, while 17% of the sample showed consistent elevated levels of externalizing behavior that persisted into adulthood. The individuals showing this pattern of persistently high externalizing behavior were significantly more likely to carry the variant of GABRA2 that was originally associated with increased risk for adult alcohol dependence in the COGA sample13 (though we note that there is inconsistency as to the risk allele across studies).39

What might be the mechanism by which GABRA2 affects risk for externalizing behavior? All of the outcomes that have been associated with GABRA2 (adult alcohol dependence, drug dependence, adult antisocial behavior, childhood conduct problems, adolescent externalizing behavior) are characterized by aspects of impulsivity.

Importantly, we find evidence that the association between GABRA2 and trajectories of externalizing behavior is moderated by parental monitoring; the effect of the genotype on externalizing behavior is stronger under conditions of lower parental monitoring and weaker under conditions of higher parental monitoring.

“Parental monitoring?” … I dunno what that exactly involves … I’m usually pretty busy just looking for the remote control.  Here is a genomic beer ad.

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