title: Genes associated with alcohol outcomes show enrichment of effects with broad externalizing and impulsivity phenotypes in an independent sample.
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.
  
  
  METHODS
  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 significant 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.
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia Department of Actuarial and Risk Management, Faculty of Business, Karabuk University, Karabuk, Turkey.
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Howard
authors.initials: H
authors.lastname: Edenberg
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, Department of Psychology, Virginia Commonwealth University, Richmond, Virginia Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000987:Antisocial Personality Disorder / Q000453:epidemiology / Q000235:genetics; D002648:Child; D019955:Conduct Disorder / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult