title: Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
abstract: BACKGROUND
  Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.
  
  
  OBJECTIVE
  To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.
  
  
  METHODS
  Primary data.
  
  
  METHODS
  Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.
  
  
  METHODS
  Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.
  
  
  RESULTS
  Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01).
  
  
  CONCLUSIONS
  These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
authors.affiliation: Washington University School of Medicine, St Louis, Missouri, USA.
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mesh_terms: D000293:Adolescent; D041923:Adolescent Development / Q000187:drug effects; D000328:Adult; D017668:Age of Onset; D005060:Europe / Q000453:epidemiology; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009538:Nicotine / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics / Q000523:psychology
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D009538:Nicotine