title: Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with 'pleasurable buzz' during early experimentation with smoking.
abstract: OBJECTIVE
  To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes.
  
  
  METHODS
  Case-control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls).
  
  
  METHODS
  Cases had smoked > or = five cigarettes/day for > or = 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life-time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study.
  
  
  RESULTS
  A non-synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5, P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6, P = 0.01); these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001).
  
  
  CONCLUSIONS
  We replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sherva
authors.forename: Kirk
authors.initials: K
authors.lastname: Wilhelmsen
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Pomerleau
authors.forename: Scott A
authors.initials: SA
authors.lastname: Chasse
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Sandy M
authors.initials: SM
authors.lastname: Snedecor
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Neuman
authors.forename: Ovide F
authors.initials: OF
authors.lastname: Pomerleau
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012677:Sensation / Q000187:drug effects*; D012907:Smoking / Q000235:genetics*; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000235:genetics / Q000523:psychology
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
references.citation: Addiction. 2003 Jan;98(1):23-31
references.pmid: 12492752
references.citation: Nature. 2008 Apr 3;452(7187):633-7
references.pmid: 18385738
references.citation: J Addict Dis. 1999;18(3):13-9
references.pmid: 10507578
references.citation: Nicotine Tob Res. 1999;1 Suppl 2:S51-7; discussion S69-70
references.pmid: 11768187
references.citation: Mol Psychiatry. 2008 Apr;13(4):368-73
references.pmid: 18227835
references.citation: Nicotine Tob Res. 2005 Feb;7(1):91-102
references.pmid: 15804681
references.citation: J Pharmacol Exp Ther. 1998 Mar;284(3):1104-11
references.pmid: 9495872
references.citation: Am J Hum Genet. 2000 Nov;67(5):1219-31
references.pmid: 11032786
references.citation: Nature. 2008 Apr 3;452(7187):638-642
references.pmid: 18385739
references.citation: Mol Pharmacol. 2003 May;63(5):1059-66
references.pmid: 12695534
references.citation: N Engl J Med. 1992 Sep 17;327(12):829-33
references.pmid: 1508241
references.citation: Am J Hum Genet. 2005 May;76(5):859-64
references.pmid: 15759211
references.citation: Addict Behav. 2005 Mar;30(3):607-11
references.pmid: 15718080
references.citation: Addict Behav. 2005 Mar;30(3):613-7
references.pmid: 15718081
references.citation: Am J Med Genet A. 2004 Jan 1;124A(1):19-27
references.pmid: 14679582
references.citation: Hum Mol Genet. 2008 Mar 1;17(5):724-34
references.pmid: 18055561
references.citation: Am J Epidemiol. 1977 Sep;106(3):203-14
references.pmid: 900119
references.citation: Psychol Med. 2004 Jul;34(5):865-79
references.pmid: 15500307
references.citation: BMC Genet. 2003 Dec 31;4 Suppl 1:S103
references.pmid: 14975171
references.citation: Addiction. 1998 Apr;93(4):595-9
references.pmid: 9684398
references.citation: Addict Behav. 2004 Feb;29(2):261-72
references.pmid: 14732415
references.citation: Hum Mol Genet. 2007 Jan 1;16(1):36-49
references.pmid: 17135278
references.citation: Nat Genet. 2008 May;40(5):616-22
references.pmid: 18385676
references.citation: Nicotine Tob Res. 2003 Aug;5(4):455-63
references.pmid: 12959783
references.citation: Br J Addict. 1991 Sep;86(9):1119-27
references.pmid: 1932883
references.citation: Hum Mol Genet. 2005 May 1;14(9):1211-9
references.pmid: 15790597
references.citation: Behav Genet. 1999 Nov;29(6):423-31
references.pmid: 10857247
references.citation: Curr Psychiatry Rep. 2007 Oct;9(5):349-57
references.pmid: 17915073
references.citation: Hum Mol Genet. 2007 Jan 1;16(1):24-35
references.pmid: 17158188
references.citation: Arch Gen Psychiatry. 1999 Jul;56(7):655-61
references.pmid: 10401514
references.citation: Am J Hum Genet. 2004 Jul;75(1):112-21
references.pmid: 15154117
references.citation: Nicotine Tob Res. 2008 Feb;10(2):287-99
references.pmid: 18236293
references.citation: Addict Behav. 1993 Jan-Feb;18(1):19-34
references.pmid: 8465673
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):94-101
references.pmid: 15211640
references.citation: Behav Genet. 1995 Mar;25(2):161-77
references.pmid: 7733857
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references.pmid: 12883005
references.citation: Genetics. 2000 Jun;155(2):945-59
references.pmid: 10835412
references.citation: Physiol Genomics. 2004 Apr 13;17(2):221-9
references.pmid: 14996991
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):354-60
references.pmid: 16671072
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144B(5):596-604
references.pmid: 17226798