title: Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.
abstract: BACKGROUND
  The CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported smoking behavior and also harbors the strongest genetic associations with chronic obstructive pulmonary disease (COPD) and lung cancer. Because the associations with lung disease remain after adjustment for self-reported smoking behaviors, it has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung cancer susceptibility independently of their effects on smoking.
  
  
  OBJECTIVE
  To compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of current cigarette exposure, with self-reported smoking behaviors.
  
  
  METHODS
  A total of 1,521 European American and 247 African American current smokers recruited into smoking cessation studies were assessed for CO at intake before smoking cessation. DNA samples were genotyped using the Illumina Omni2.5 microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked per day, Fagerstrom test for nicotine dependence) were studied.
  
  
  RESULTS
  Variants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a nonsynonymous variant in CHRNA5, are genomewide association study-significantly associated with CO (β = 2.66; 95% confidence interval [CI], 1.74-3.58; P = 1.65 × 10(-8)), and this association remains strong after adjusting for smoking behavior (β = 2.18; 95% CI, 1.32-3.04; P = 7.47 × 10(-7)). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 × 10(-4)) in African Americans (r = 0.14; 95% CI, 0.02-0.26; P = 0.003) than in European-Americans (r = 0.36; 95% CI, 0.31-0.40; P = 0.0001).
  
  
  CONCLUSIONS
  Exhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.
authors: 1 Department of Psychiatry, and.
authors: A Joseph
authors: AJ
authors: Bloom
authors: Sarah M
authors: SM
authors: Hartz
authors: Timothy B
authors: TB
authors: Baker
authors: Li-Shiun
authors: LS
authors: Chen
authors: Megan E
authors: ME
authors: Piper
authors: Louis
authors: L
authors: Fox
authors: Maribel
authors: M
authors: Martinez
authors: Dorothy
authors: D
authors: Hatsukami
authors: Eric O
authors: EO
authors: Johnson
authors: Cathy C
authors: CC
authors: Laurie
authors: Nancy L
authors: NL
authors: Saccone
authors: Alison
authors: A
authors: Goate
authors: Laura J
authors: LJ
authors: Bierut
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D002248:Carbon Monoxide / Q000032:analysis*; D016001:Confidence Intervals; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000208:ethnology / Q000235:genetics* / Q000523:psychology; D016540:Smoking Cessation / Q000208:ethnology / Q000379:methods* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000208:ethnology / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D015415:Biomarkers; C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D002248:Carbon Monoxide; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6
keywords: chronic obstructive pulmonary disease; lung cancer; nicotine; nicotinic receptor; smoking