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Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems
S Villafuerte1, V Strumba, S F Stoltenberg
1Molecular & Behavioral Neuroscience Institute, University of Michigan, 109 Zina Pitcher Place, BSRB 5063, Ann Arbor, MI 48109–2200, USA. svillafu@umich.edu
Genes, Brain, and Behavior
|April 10, 2013
Summary
Genetic variants in the GABRA2 gene are linked to impulsiveness and problem drinking. These GABRA2 gene variations influence impulsiveness, which in turn affects alcohol problem development.
Area of Science:
- Neurogenetics
- Behavioral Genetics
- Psychiatric Genetics
Background:
- Genetic variants in GABRA2 are associated with alcohol use, electroencephalography (EEG) beta waves, and impulsiveness.
- Impulsiveness is a recognized behavioral risk factor for alcohol and substance abuse.
Purpose of the Study:
- To investigate the association between 11 GABRA2 variants and NEO-impulsiveness and problem drinking.
- To explore the mediating role of impulsiveness in the relationship between GABRA2 and alcohol problems.
Main Methods:
- Examined 11 single-nucleotide polymorphisms (SNPs) in the GABRA2 gene in 295 adult subjects.
- Assessed NEO-impulsiveness and Lifetime Alcohol Problems Score (LAPS).
- Utilized linkage disequilibrium (LD) and conditional analyses to identify genetic signals.
Main Results:
- Ten GABRA2 SNPs were significantly associated with NEO-impulsiveness (P < 0.03).
- Four SNPs and a specific haplotype were associated with LAPS (P < 0.03).
- Impulsiveness partially mediated the relationship between GABRA2 and LAPS (22.6% on average).
Conclusions:
- GABRA2 variation, particularly in the intron 3 to intron 4 region, is associated with impulsiveness.
- This association partially influences the development of alcohol problems, suggesting a mediating role for impulsiveness.
- A potential functional SNP (rs279827) near a splice site may underlie these observed associations.
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