Examination of rare missense variants in the CHRNA5-A3-B4 gene cluster to level of response to alcohol in the San Diego Sibling Pair study.
- Authors
- Choquet, Hélène; Joslyn, Geoff; Lee, Andrew; Kasberger, Jay; Robertson, Margaret; Brush, Gerry; Schuckit, Marc A; White, Ray; Jorgenson, Eric
- Year
- 2013
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 23458267
- DOI
- 10.1111/acer.12099
BACKGROUND: Common variants in the CHRNA5-A3-B4 gene cluster have been shown to be associated with nicotine dependence and alcohol use disorders (AUDs) and related traits, including the level of response (LR) to alcohol. Recently, rare variants (MAF < 0.05) in CHRNB4 have been reported to be associated with a decreased risk of developing nicotine dependence. However, the role of rare variants in the CHRNA5-A3-B4 gene cluster to the LR to alcohol has not yet been established. METHODS: To determine whether rare variants in the CHRNA5-A3-B4 gene cluster contribute to the LR to alcohol, the coding regions of these 3 genes were sequenced in 538 subjects from the San Diego Sibling Pair study. RESULTS: The analyses identified 16 rare missense variants, 9 of which were predicted to be damaging using in silico analysis tools. Carriers of these variants were compared to noncarriers using a family-based design for each gene and for the gene cluster as a whole. In these analyses, a CHRNA5 carrier status was significantly associated with the phenotype related to the feeling of intoxication experienced during the alcohol challenge (p = 0.039). CONCLUSIONS: These results indicate that rare genetic variation in the CHRNA5-A3-B4 gene cluster contributes modestly to the LR to alcohol in the San Diego Sibling Pair study and may protect against AUDs. However, replication studies are needed to confirm our findings.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Body Mass Index Is Inversely Associated With Level of Response to Alcohol: Role of Total Body Water. | Vergeer RR et al. | β | 2025 | β |
| Mutation of the Ξ±5 nicotinic acetylcholine receptor subunit increases ethanol and nicotine consumption in adolescence and impacts adult drug consumption. | Quijano CardΓ© NA et al. | β | 2022 | β |
| Reduced expression of ethanol sensitization by Ξ±3Ξ²4 nicotinic acetylcholine receptors in DBA/2J mice. | Miller CN et al. | β | 2020 | β |
| The role of nicotinic acetylcholine receptors in alcohol-related behaviors. | Miller CN et al. | β | 2020 | β |
| Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior. | Deak JD et al. | β | 2019 | β |
| The Ξ±3Ξ²4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL/6J mice. | Miller CN et al. | β | 2019 | β |
| A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity. | Schuckit MA | β | 2018 | β |
| Knockout of alpha 5 nicotinic acetylcholine receptors subunit alters ethanol-mediated behavioral effects and reward in mice. | Dawson A et al. | β | 2018 | β |
| No evidence of a role of the Ξ²4 subunit of the nicotinic acetylcholine receptor in alcohol-related behaviors. | Kamens HM et al. | β | 2017 | β |
| Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism. | Rahman S et al. | β | 2016 | β |
| Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder. | Grotewiel M et al. | β | 2015 | β |
| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | Salvatore JE et al. | β | 2015 | β |
| Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine. | Perez E et al. | β | 2015 | β |
| A brief history of research on the genetics of alcohol and other drug use disorders. | Schuckit MA | β | 2014 | β |