Posts Tagged ‘Alcoholism’

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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Where da rodents kick it
Image by Scrunchleface via Flickr

A recent GWAS study identified the 3′ region of the liver- (not brain) expressed PECR gene (rs7590720(G) and rs1344694(T)) on chromosome 2 as a risk factor for alcohol dependency.  These results, as reported by Treutlein et al., in “Genome-wide Association Study of Alcohol Dependence” were based on a population of 487 male inpatients and a follow-up re-test in a population of 1024 male inpatients and 996 control participants.

The authors also asked whether lab rats who – given the choice between water-based and ethanol-spiked beverages over the course of 1 year – showed differential gene expression in those rats that were alcohol preferrers vs. alcohol non-preferring rats.  Among a total of 542 genes that were found to be differentially expressed in the amygdala and caudate nucleus of alcohol vs. non-alcohol-preferring rat strains,  a mere 3 genes – that is the human orthologs of these 3 genes – did also show significant association with alcohol dependency in the human populations.  Here are the “rat genes” (ie. human homologs that show differential expression in rats and association with alcohol dependency in humans): rs1614972(C) in the alcohol dehydrogenase 1C (ADH1C) gene, rs13273672(C) in the GATA binding protein 4 (GATA4) gene, and rs11640875(A) in the cadherin 13 (CDH13) gene.

My 23andMe profile gives a mixed AG at rs7590720, and a mixed GT at rs1344694 while I show a mixed CT at rs1614972, CT at rs13273672 and AG at rs11640875.  Boooring! a middling heterozygote at all 5 alcohol prefer/dependency loci.   Were these the loci for chocolate prefer/dependency I would be a full risk-bearing homozygote.


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