Journal article
A GABRA2 polymorphism improves a model for prediction of drinking initiation
Alcohol (Fayetteville, N.Y.), Vol.63, pp.1-8
09/2017
DOI: 10.1016/j.alcohol.2017.03.003
PMCID: PMC5657392
PMID: 28847377
Abstract
Survival analysis was used to explore the addition of a single nucleotide polymorphism (SNP) and covariates (sex, interview age, and ancestry) on a previously published model's ability to predict onset of drinking. A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking.
A subsample of 674 adolescents (ages 14–17) participating in the Collaborative Study on the Genetics of Alcoholism (COGA) was examined using a previously derived Cox proportional hazards model containing: 1) number of non-drinking related conduct disorder (CD) symptoms, 2) membership in a high-risk alcohol-dependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach Youth Self Report (YSR) externalizing score, and 5) YSR social problems score. The above covariates along with the SNP variant of GABRA2, rs279871, were added to this model. Five new prototype models were examined. The most parsimonious model was chosen based on likelihood ratio tests and model fit statistics.
The final model contained four of the five original predictors (YSR social problems score was no longer significant and hence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (two copies of the high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype were more likely to begin drinking than those without this genotype.
The joint effect of the gene (rs279871 TT genotype) and environment (MBFD) on adolescent alcohol initiation is additive, but not interactive, after controlling for behavior problems (CD and YSR externalizing score). This suggests that the impact of the high-risk TT genotype on the onset of drinking is affected by controlling for peer drinking and does not include genotype-by-environment interactions.
•A rs279871 SNP is associated with increased risk for problematic alcohol use.•This SNP is associated with behavior that is related to early alcohol initiation.•A TT genotype of this SNP improved a previous model for alcohol initiation.•Adolescents with the TT genotype were more likely to begin drinking earlier.•The impact of the TT genotype is affected by controlling for peer drinking.
Details
- Title: Subtitle
- A GABRA2 polymorphism improves a model for prediction of drinking initiation
- Creators
- Samuel Kuperman - University of IowaGrace Chan - UConn HealthJohn Kramer - University of IowaLeah Wetherill - Indiana UniversityLaura Acion - University of IowaHoward J. Edenberg - Indiana UniversityTatiana M. Foroud - Indiana UniversityJohn Nurnberger - Indiana UniversityArpana Agrawal - Washington University in St. LouisAndrey Anokhin - Washington University in St. LouisAndrew Brooks - Rutgers, The State University of New JerseyVictor Hesselbrock - UConn HealthMichie Hesselbrock - UConn HealthMarc Schuckit - University of California San DiegoJay Tischfield - Rutgers, The State University of New JerseyXiangtao Liu - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Alcohol (Fayetteville, N.Y.), Vol.63, pp.1-8
- DOI
- 10.1016/j.alcohol.2017.03.003
- PMID
- 28847377
- PMCID
- PMC5657392
- NLM abbreviation
- Alcohol
- ISSN
- 0741-8329
- eISSN
- 1873-6823
- Publisher
- Elsevier
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293758202771
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