title: Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry.
abstract: OBJECTIVE
  Genetic studies of alcohol dependence (AD) have identified several candidate loci and genes, but most observed effects are small and difficult to reproduce. A plausible explanation for inconsistent findings may be a violation of the assumption that genetic factors contributing to each of the seven DSM-IV criteria point to a single underlying dimension of risk. Given that recent twin studies suggest that the genetic architecture of AD is complex and probably involves multiple discrete genetic factors, the current study employed common single nucleotide polymorphisms in two multivariate genetic models to examine the assumption that the genetic risk underlying DSM-IV AD is unitary.
  
  
  METHODS
  AD symptoms and genome-wide single nucleotide polymorphism (SNP) data from 2596 individuals of European descent from the Study of Addiction: Genetics and Environment were analyzed using genomic-relatedness-matrix restricted maximum likelihood. DSM-IV AD symptom covariance was described using two multivariate genetic factor models.
  
  
  RESULTS
  Common SNPs explained 30% (standard error=0.136, P=0.012) of the variance in AD diagnosis. Additive genetic effects varied across AD symptoms. The common pathway model approach suggested that symptoms could be described by a single latent variable that had a SNP heritability of 31% (0.130, P=0.008). Similarly, the exploratory genetic factor model approach suggested that the genetic variance/covariance across symptoms could be represented by a single genetic factor that accounted for at least 60% of the genetic variance in any one symptom.
  
  
  CONCLUSIONS
  Additive genetic effects on DSM-IV alcohol dependence criteria overlap. The assumption of common genetic effects across alcohol dependence symptoms appears to be a valid assumption.
authors.affiliation: Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.|Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.
authors.forename: Rohan H C
authors.initials: RH
authors.lastname: Palmer
authors.affiliation: Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.|Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.|Providence Veterans Affairs Medical Center, Providence, RI, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: McGeary
authors.affiliation: Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.affiliation: Department of Psychology and Neuroscience and Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Keller
authors.affiliation: Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Brick
authors.affiliation: Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.|Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Knopik
mesh_terms: D000328:Adult; D064829:Alcohol Abstinence; D000437:Alcoholism / Q000208:ethnology / Q000235:genetics* / Q000534:rehabilitation; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005163:Factor Analysis, Statistical; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D044465:White People / Q000208:ethnology / Q000235:genetics*
keywords: Alcohol dependence; DSM-IV; GCTA; alcoholism; diagnostic criteria; genetics