Genes associated with alcohol outcomes show enrichment of effects with broad externalizing and impulsivity phenotypes in an independent sample

Fazil Aliev, Leah Wetherill, Laura Bierut, Kathleen K. Bucholz, Howard Edenberg, Tatiana Foroud, Coga Investigators, Xiaoling Xuei

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: The purpose of this study was to evaluate evidence for association with a panel of genes previously associated with alcohol-related traits in a new sample of adolescent and young adult individuals (N = 2,128; 51% female) collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). We tested for association with phenotypes related to externalizing behavior, including diagnostic symptom counts for disorders on the externalizing spectrum (alcohol dependence, conduct disorder, adult antisocial personality disorder, and illicit drug dependence), and related behavioral/personality traits (Achenbach Externalizing, NEO Extraversion, NEO Conscientiousness, Zuckerman’s Sensation Seeking, and the Barratt Impulsivity Scale) based on the substantial literature suggesting that these behaviors may be alternate manifestations of a shared genetic liability.

Method: We tested for overall enrichment of the set of 215 genotyped single-nucleotide polymorphisms (SNPs) for each of the phenotypes. We conducted secondary analyses comparing results for sensation seeking with results for the other phenotypes.

Results: For all phenotypes, there was signifi- cant enrichment of association results (p <.05) compared with chance expectations. The greatest number of significant results was observed with the phenotype Sensation Seeking. Secondary analyses indicated that the number of SNPs yielding p <.05 with Sensation Seeking was significantly greater than that observed for each of the other phenotypes.

Conclusions: We find evidence for enrichment of association results across a spectrum of externalizing phenotypes with a panel of candidate genes/SNPs selected based on previous suggestion of association with alcohol-related outcomes. In particular, we find significant enrichment of effects with sensation seeking, suggesting that this may be a particularly salient behavior associated with risk for alcohol-related problems.

Original languageEnglish
Pages (from-to)38-46
Number of pages9
JournalJournal of Studies on Alcohol and Drugs
Volume76
Issue number1
StatePublished - Jan 1 2015

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Impulsive Behavior
Genes
Polymorphism
alcohol
Alcohols
Phenotype
Nucleotides
Single Nucleotide Polymorphism
drug dependence
personality disorder
Street Drugs
Alcoholism
personality traits
alcoholism
liability
evidence
young adult
diagnostic
candidacy
Antisocial Personality Disorder

ASJC Scopus subject areas

  • Health(social science)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Genes associated with alcohol outcomes show enrichment of effects with broad externalizing and impulsivity phenotypes in an independent sample. / Aliev, Fazil; Wetherill, Leah; Bierut, Laura; Bucholz, Kathleen K.; Edenberg, Howard; Foroud, Tatiana; Investigators, Coga; Xuei, Xiaoling.

In: Journal of Studies on Alcohol and Drugs, Vol. 76, No. 1, 01.01.2015, p. 38-46.

Research output: Contribution to journalArticle

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N2 - Objective: The purpose of this study was to evaluate evidence for association with a panel of genes previously associated with alcohol-related traits in a new sample of adolescent and young adult individuals (N = 2,128; 51% female) collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). We tested for association with phenotypes related to externalizing behavior, including diagnostic symptom counts for disorders on the externalizing spectrum (alcohol dependence, conduct disorder, adult antisocial personality disorder, and illicit drug dependence), and related behavioral/personality traits (Achenbach Externalizing, NEO Extraversion, NEO Conscientiousness, Zuckerman’s Sensation Seeking, and the Barratt Impulsivity Scale) based on the substantial literature suggesting that these behaviors may be alternate manifestations of a shared genetic liability.Method: We tested for overall enrichment of the set of 215 genotyped single-nucleotide polymorphisms (SNPs) for each of the phenotypes. We conducted secondary analyses comparing results for sensation seeking with results for the other phenotypes.Results: For all phenotypes, there was signifi- cant enrichment of association results (p <.05) compared with chance expectations. The greatest number of significant results was observed with the phenotype Sensation Seeking. Secondary analyses indicated that the number of SNPs yielding p <.05 with Sensation Seeking was significantly greater than that observed for each of the other phenotypes.Conclusions: We find evidence for enrichment of association results across a spectrum of externalizing phenotypes with a panel of candidate genes/SNPs selected based on previous suggestion of association with alcohol-related outcomes. In particular, we find significant enrichment of effects with sensation seeking, suggesting that this may be a particularly salient behavior associated with risk for alcohol-related problems.

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