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Commentary| Volume 64, ISSUE 11, P919-921, December 01, 2008

Genetics of Smoking Behavior and Its Consequences: The Role of Nicotinic Acetylcholine Receptors

DOI:https://doi.org/10.1016/j.biopsych.2008.09.010
Genetics of Smoking Behavior and Its Consequences: The Role of Nicotinic Acetylcholine Receptors
Previous ArticleIn this Issue-December 1st
Next ArticleA Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence
      Biological psychiatry seeks to understand brain biology and its role in behavior and to use the knowledge for treatment of individuals troubled by their own actions or the content of their consciousness. Nicotinic acetylcholine receptors (nAChRs) symbolize both the principle on which the discipline is founded and its mission, binding both acetylcholine, the first neurotransmitter, and nicotine, a substance with particular appeal to those the field seeks to help, with epic consequences on behavior and health. Recent genetic studies have revealed solid evidence that sequence variants within a cluster of nAChR genes on chromosome 15 correlate with smoking behavior and nicotine dependence (ND) (
      • Saccone S.F.
      • Hinrichs A.L.
      • Saccone N.L.
      • Chase G.A.
      • Konvicka K.
      • Madden P.A.
      Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.
      Hum Mol Genet. 2007; 16: 36-49
      ,
      • Berrettini W.
      • Yuan X.
      • Tozzi F.
      • Song K.
      • Francks C.
      • Chilcoat H.
      • et al.
      Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking.
      Mol Psychiatry. 2008; 13: 368-373
      ,
      • Thorgeirsson T.E.
      • Geller F.
      • Sulem P.
      • Rafnar T.
      • Wiste A.
      • Magnusson K.P.
      • et al.
      A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
      Nature. 2008; 452: 638-642
      ). In addition, there is unequivocal evidence of association of the same region with risk of smoking-related diseases (
      • Thorgeirsson T.E.
      • Geller F.
      • Sulem P.
      • Rafnar T.
      • Wiste A.
      • Magnusson K.P.
      • et al.
      A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
      Nature. 2008; 452: 638-642
      ,
      • Amos C.I.
      • Wu X.
      • Broderick P.
      • Gorlov I.P.
      • Gu J.
      • Eisen T.
      • et al.
      Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.
      Nat Genet. 2008; 40: 616-622
      ,
      • Hung R.J.
      • McKay J.D.
      • Gaborieau V.
      • Boffetta P.
      • Hashibe M.
      • Zaridze D.
      • et al.
      A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.
      Nature. 2008; 452: 633-637
      ). How these findings are connected is a subject of some debate. An article by Grucza et al., appearing in this issue of Biological Psychiatry (pages 922–929), brings another twist to this story, suggesting that the variant most solidly associated with smoking-related phenotypes protects against cocaine dependence (
      • Grucza R.A.
      • Wang J.C.
      • Stitzel J.A.
      • Hinrichs A.L.
      • Saccone S.F.
      • Saccone N.L.
      • et al.
      A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.
      Biol Psychiatry. 2008; 64: 922-929
      ).
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      References

        • Saccone S.F.
        • Hinrichs A.L.
        • Saccone N.L.
        • Chase G.A.
        • Konvicka K.
        • Madden P.A.
        Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.
        Hum Mol Genet. 2007; 16: 36-49
        View in Article
        • Berrettini W.
        • Yuan X.
        • Tozzi F.
        • Song K.
        • Francks C.
        • Chilcoat H.
        • et al.
        Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking.
        Mol Psychiatry. 2008; 13: 368-373
        View in Article
        • Thorgeirsson T.E.
        • Geller F.
        • Sulem P.
        • Rafnar T.
        • Wiste A.
        • Magnusson K.P.
        • et al.
        A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.
        Nature. 2008; 452: 638-642
        View in Article
        • Amos C.I.
        • Wu X.
        • Broderick P.
        • Gorlov I.P.
        • Gu J.
        • Eisen T.
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        Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.
        Nat Genet. 2008; 40: 616-622
        View in Article
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        • McKay J.D.
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        • Zaridze D.
        • et al.
        A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.
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        Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence.
        Mol Psychiatry. 2008; ([published online ahead of print April 15])
        View in Article

      Article info

      Publication history

      Accepted: September 13, 2008
      Received: September 12, 2008

      Identification

      DOI: https://doi.org/10.1016/j.biopsych.2008.09.010

      Copyright

      © 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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