A GABRA2 Polymorphism Improves a Model for Prediction of Drinking Initiation

S KUPERMAN; G CHAN; J KRAMER; L WETHERILL; L ACION; H EDENBERG; T FOROUD; J NURNBERGER; A AGRAWAL; A ANOKHIN; A BROOKS; V HESSELBROCK; M HESSELBROCK; M SCHUCKIT; J TISCHFIELD; X LIU

ALCOHOL

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2017

0741-8329

Background:   Survival analysis was used to explore theaddition of a single nucleotide polymorphism (SNP) and covariates (sex,interview age, and ancestry) on a previously published model?s ability topredict onset of drinking.  A SNP variantof rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor(GABRA2), was selected due to itsassociations with alcoholism in young adults and with behaviors that increasedrisk for early drinking.  Methods:A subsample of 674 adolescents (ages 14-17) participating in the CollaborativeStudy on the Genetics of Alcoholism (COGA) was examined using a previouslyderived Cox proportional hazards model containing: 1) number of non-drinkingrelated conduct disorder (CD) symptoms, 2) membership in a high-risk alcoholdependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach YouthSelf Report (YSR) externalizing score, and 5) YSR social problems score.  The above covariates along with the SNPvariant of GABRA2, rs279871 wereadded to this model.  Five new prototypemodels were examined. The most parsimonious model was chosen based onlikelihood ratio tests and model fit statistics.  Results:  The final model contained four of the fiveoriginal predictors (YSR social problems score was no longer significant andhence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (2 copies ofthe high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype weremore 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 initiationis additive, but not interactive, after controlling for behavior problems (CDand YSR-externalizing score).  Thissuggests that the impact of the high-risk TT genotype on the onset of drinkingis affected by controlling for peer drinking and does not include a genotype byenvironment interactions.