title: Associations and interactions between SNPs in the alcohol metabolizing genes and alcoholism phenotypes in European Americans.
abstract: BACKGROUND
  Alcohol dependence is a major cause of morbidity and mortality worldwide and has a strong familial component. Several linkage and association studies have identified chromosomal regions and/or genes that affect alcohol consumption, notably in genes involved in the 2-stage pathway of alcohol metabolism.
  
  
  METHODS
  Here, we use multiple regression models to test for associations and interactions between 2 alcohol-related phenotypes and SNPs in 17 genes involved in alcohol metabolism in a sample of 1,588 European American subjects.
  
  
  RESULTS
  The strongest evidence for association after correcting for multiple testing was between rs1229984, a nonsynonymous coding SNP in ADH1B, and DSM-IV symptom count (p = 0.0003). This SNP was also associated with maximum number of drinks in 24 hours (p = 0.0004). Each minor allele at this SNP predicts 45% fewer DSM-IV symptoms and 18% fewer max drinks. Another SNP in a splice site in ALDH1A1 (rs8187974) showed evidence for association with both phenotypes as well (p = 0.02 and 0.004, respectively), but neither association was significant after accounting for multiple testing. Minor alleles at this SNP predict greater alcohol consumption. In addition, pairwise interactions were observed between SNPs in several genes (p = 0.00002).
  
  
  CONCLUSIONS
  We replicated the large effect of rs1229984 on alcohol behavior, and although not common (MAF = 4%), this polymorphism may be highly relevant from a public health perspective in European Americans. Another SNP, rs8187974, may also affect alcohol behavior but requires replication. Also, interactions between polymorphisms in genes involved in alcohol metabolism are likely determinants of the parameters that ultimately affect alcohol consumption.
authors.affiliation: The Genetics Program, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sherva
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Neuman
authors.forename: Nanette
authors.initials: N
authors.lastname: Rochberg
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Saccone
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000235:genetics; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D000426:Alcohol Dehydrogenase