The present study suggests that both rare and common variant associations in GABRA2 confer risk for alcohol use disorder and antisocial behaviors, indicating a potential liability toward externalizing behavior more broadly.
Differences in intervention effects by GABRA2 genotype were most pronounced from ages 13 to 16-a period when drinking is associated with increased risk for alcohol use disorder.
GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABA<sub>A</sub> interneuron activity and beta oscillations.
For the BAES stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with 2 copies of the GABRA2rs279858 C "risk" allele for AUD exhibited the greatest stimulant responses to high-dose alcohol compared to the other risk allele counts (dose-by-allele count interaction effect, p = 0.001, post hoc contrast for C-allele, p = 0.012).
The purpose of the present study was to examine the effects of GABRA2 genotype and stressful life events on aggressive behaviour, alcohol use frequency and occurrence of alcohol use disorder in a population representative sample of adolescents followed up from third grade to 25 years of age.
More recent studies in family-based samples have implicated GABRA2, nicotinic receptor genes such as CHRNB3, and a number of other specific single genes as associated with alcohol use disorders.
Our findings provide further evidence that variation within GABRA2 is associated with attenuated negative responses to alcohol, a known risk factor for vulnerability to alcohol use disorders.
These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol.
Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems, controls and available first degree relatives.
In both the Plains Indians and the Caucasians: (1) the GABRG1 haplotype block(s) did not extend to GABRA2; (2) GABRG1 haplotypes and SNPs were significantly associated with AUD; (3) there was no association between GABRA2 haplotypes and AUD; (4) there were several common (>or=0.05) haplotypes that spanned GABRG1 and GABRA2 (341 kb), three of which were present in both populations: one of these ancestral haplotypes was associated with AUD, the other two were more common in non-alcoholics; this association was determined by GABRG1; (5) in the Finns, three less common (<0.05) extended haplotypes showed an association with AUD that was determined by GABRA2.