A GABRA2 polymorphism improves a model for prediction of drinking initiation

Samuel Kuperman, Grace Chan, John Kramer, Leah Wetherill, Laura Acion, Howard Edenberg, Tatiana Foroud, John Nurnberger, Arpana Agrawal, Andrey Anokhin, Andrew Brooks, Victor Hesselbrock, Michie Hesselbrock, Marc Schuckit, Jay Tischfield, Xiangtao Liu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalAlcohol
Volume63
DOIs
StatePublished - Sep 1 2017

Fingerprint

Polymorphism
Drinking
Genotype
Self Report
Single Nucleotide Polymorphism
Conduct Disorder
Social Problems
Alcoholism
Nucleotides
adolescent
alcoholism
Alcohols
Chromosomes, Human, Pair 4
Aptitude
GABA Receptors
Thymine
alcohol
Survival Analysis
Risk-Taking
Proportional Hazards Models

Keywords

  • Adolescent
  • Alcohol
  • Drinking initiation
  • GABRA2
  • Rs279871
  • Survival analysis modeling

ASJC Scopus subject areas

  • Health(social science)
  • Medicine(all)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

Kuperman, S., Chan, G., Kramer, J., Wetherill, L., Acion, L., Edenberg, H., ... Liu, X. (2017). A GABRA2 polymorphism improves a model for prediction of drinking initiation. Alcohol, 63, 1-8. https://doi.org/10.1016/j.alcohol.2017.03.003

A GABRA2 polymorphism improves a model for prediction of drinking initiation. / Kuperman, Samuel; Chan, Grace; Kramer, John; Wetherill, Leah; Acion, Laura; Edenberg, Howard; Foroud, Tatiana; Nurnberger, John; Agrawal, Arpana; Anokhin, Andrey; Brooks, Andrew; Hesselbrock, Victor; Hesselbrock, Michie; Schuckit, Marc; Tischfield, Jay; Liu, Xiangtao.

In: Alcohol, Vol. 63, 01.09.2017, p. 1-8.

Research output: Contribution to journalArticle

Kuperman, S, Chan, G, Kramer, J, Wetherill, L, Acion, L, Edenberg, H, Foroud, T, Nurnberger, J, Agrawal, A, Anokhin, A, Brooks, A, Hesselbrock, V, Hesselbrock, M, Schuckit, M, Tischfield, J & Liu, X 2017, 'A GABRA2 polymorphism improves a model for prediction of drinking initiation', Alcohol, vol. 63, pp. 1-8. https://doi.org/10.1016/j.alcohol.2017.03.003
Kuperman, Samuel ; Chan, Grace ; Kramer, John ; Wetherill, Leah ; Acion, Laura ; Edenberg, Howard ; Foroud, Tatiana ; Nurnberger, John ; Agrawal, Arpana ; Anokhin, Andrey ; Brooks, Andrew ; Hesselbrock, Victor ; Hesselbrock, Michie ; Schuckit, Marc ; Tischfield, Jay ; Liu, Xiangtao. / A GABRA2 polymorphism improves a model for prediction of drinking initiation. In: Alcohol. 2017 ; Vol. 63. pp. 1-8.
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abstract = "Background 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. Methods 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. Results 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. Conclusions 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.",
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AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Nurnberger, John

AU - Agrawal, Arpana

AU - Anokhin, Andrey

AU - Brooks, Andrew

AU - Hesselbrock, Victor

AU - Hesselbrock, Michie

AU - Schuckit, Marc

AU - Tischfield, Jay

AU - Liu, Xiangtao

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N2 - Background 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. Methods 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. Results 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. Conclusions 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.

AB - Background 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. Methods 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. Results 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. Conclusions 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.

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