title: Different phenotypic and genotypic presentations in alcohol dependence: age at onset matters.
abstract: OBJECTIVE
  Several theoretical typology models have been proposed to classify alcoholism into more homogeneous subtypes using various criteria, for which age at onset of alcohol dependence is shared across many models. We investigated the evidence for the distinction between early- versus late-onset alcoholism by examining relevant phenotypic and genotypic variables.
  
  
  METHODS
  Data are from 1,248 individuals with alcohol dependence, who were interviewed to collect detailed clinical information. Early versus late onset of alcohol dependence was defined by the age at onset of 22 years. Odds ratio (OR) and Cohen's d were calculated as effect size for comparisons of clinical features between the two groups. We adjusted interviewed age and gender in logistic regression models. Case-control genetic analyses were conducted for the association between HTR1B, SLC6A4, DRD2, and OPRμ1 genes and subgroups of alcohol dependence using a sample of 530 controls screened for alcohol problems.
  
  
  RESULTS
  Early-onset alcoholism exhibited significantly (p < .01) different clinical characteristics from late-onset alcoholism, including higher severity in alcohol dependence symptoms (d = 0.22) and maximum drinking quantity within 24 hours (d = 0.40), more rapid progression from regular drinking to meet alcohol dependence diagnosis (d = 1.73), higher expectancies for alcohol (d = 0.22-0.47), more comorbidity with externalizing disorders (ORs = 2.8-2.9), and greater prevalence of family alcohol use problems (d = 0.26-0.43). In addition, markers in the HTR1B and OPRμ1 genes showed genetic associations with subgroups of alcohol dependence (ORs = 1.5-2.4).
  
  
  CONCLUSIONS
  Our findings support that subgroups of alcohol dependence defined by onset age have phenotypic and genetic differences. The early-onset subgroup had more severe features for almost every aspect we examined. Coupled with genetic association findings, age at onset of alcohol dependence may serve as a simple but important clinical marker with implications for future etiological research and intervention.
authors: Department of Public Health and Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
authors: Yu-Chu
authors: YC
authors: Chen
authors: Carol A
authors: CA
authors: Prescott
authors: Dermot
authors: D
authors: Walsh
authors: Diana G
authors: DG
authors: Patterson
authors: Brien P
authors: BP
authors: Riley
authors: Kenneth S
authors: KS
authors: Kendler
authors: Po-Hsiu
authors: PH
authors: Kuo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D015415:Biomarkers; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; C470302:HTR1B protein, human; C485764:OPRM1 protein, human; D044302:Receptor, Serotonin, 5-HT1B; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins