title: Genomic influences on alcohol problems in a population-based sample of young adults.
abstract: OBJECTIVE
  Alcohol problems (AP) contribute substantially to the global disease burden. Twin and family studies suggest that AP are genetically influenced, although few studies have identified variants or genes that are robustly associated with risk. This study identifies genetic and genomic influences on AP during young adulthood, which is often when drinking habits are established.
  
  
  METHODS
  We conducted a genome-wide association study of AP. We further conducted gene-based tests, gene ontology analyses and functional genomic enrichment analyses to assess genomic factors beyond single variants that are relevant to AP.
  
  
  METHODS
  The Avon Longitudinal Study of Parents and Children, a large population-based study of a UK birth cohort.
  
  
  METHODS
  Genetic and phenotypical data were available for 4304 participants.
  
  
  METHODS
  The AP phenotype was a factor score derived from items from the Alcohol Use Disorders Identification Test, symptoms of DSM-IV alcohol dependence, and three additional problem-related items.
  
  
  RESULTS
  One variant met genome-wide significance criteria. Four out of 22,880 genes subjected to gene-based analyses survived a stringent significance threshold (q < 0.05); none of these have been implicated previously in alcohol-related phenotypes. Several biologically plausible gene ontologies were statistically over-represented among implicated single nucleotide polymorphisms (SNPs). SNPs on the Illumina 550 K SNP chip accounted for ~5% of the phenotypical variance in AP.
  
  
  CONCLUSIONS
  Genetic and genomic factors appear to play a role in alcohol problems in young adults. Genes involved in nervous system-related processes, such as signal transduction and neurogenesis, potentially contribute to liability to alcohol problems, as do genes expressed in non-brain tissues.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA,, USA.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Edwards
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Wolen
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Salvatore
authors.forename: Charles O
authors.initials: CO
authors.lastname: Gardner
authors.forename: George
authors.initials: G
authors.lastname: McMahon
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: John
authors.initials: J
authors.lastname: Macleod
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickman
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
mesh_terms: D000293:Adolescent; D019973:Alcohol-Related Disorders / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics; D005838:Genotype; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics; D006113:United Kingdom; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D002135:Calcium-Binding Proteins; D051273:Glucose Transporter Type 2; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C551025:CRACR2A protein, human; C476731:NLRP12 protein, human; C495680:SLC2A2 protein, human; C469270:TBCE protein, human
keywords: ALSPAC; Alcohol problems; GWAS; epigentic enrichment; gene-based test; polygenic