Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study.
- Authors
- Melroy, Whitney E; Stephens, Sarah H; Sakai, Joseph T; Kamens, Helen M; McQueen, Matthew B; Corley, Robin P; Stallings, Michael C; Hopfer, Christian J; Krauter, Kenneth S; Brown, Sandra A; Hewitt, John K; Ehringer, Marissa A
- Year
- 2014
- Journal
- Behavior genetics
- PMID
- 24687270
- DOI
- 10.1007/s10519-014-9653-y
- PMCID
- PMC4098655
Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility.
Study sample characteristics of the CADD and GADD. Each phenotypic variable is shown with the respective wave the data were drawn from. As CADD is a sample comprised of clinical and control subjects, variable descriptives for each are shown separately. The mean ± the standard deviation is shown for age, lifetime CD symptoms, and lifetime adolescent/young adult and adult AAD symptoms for each variable used in the analysis, as well as the sample size for each variable.
Linkage Disequilibrium (LD) plot generated by Haploview (Barrett et al. 2005) for the SNPs chosen in the CADD sample. Numbers in the boxes are r2 x 100. A) LD plot for EAs. Note that rs279858 and rs279871 are in high LD. B) LD plot for Hispanics.
Linkage Disequilibrium (LD) plot generated by Haploview (Barrett et al. 2005) for the SNPs chosen in the GADD sample. Numbers in the boxes are r2 x 100. A) LD plot for EAs. B) LD plot for Hispanics.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| GABA<sub>A</sub> Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol: Genetic and Pharmacological Evidence. | Chandler CM et al. | — | 2018 | → |
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| GABA<sub>A</sub> receptor subtype involvement in addictive behaviour. | Stephens DN et al. | — | 2017 | → |
| Unique and interactive effects of impulsivity facets on reckless driving and driving under the influence in a high-risk young adult sample. | Luk JW et al. | — | 2017 | → |
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| Risky driving and sexual behaviors as developmental outcomes of co-occurring substance use and antisocial behavior. | Luk JW et al. | — | 2016 | → |
| Genetic inactivation of midkine modulates behavioural responses to ethanol possibly by enhancing GABA(A) receptor sensitivity to GABA(A) acting drugs. | Vicente-Rodríguez M et al. | — | 2014 | → |