Publication Details

Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.

Authors:Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau O, Swan GE, Goate AM, Rutter J, Bertelsen S, Fox L, Fugman D, Martin NG, Montgomery GW, Wang JC, Ballinger DG, Rice JP, Bierut LJ
Title:Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs.
Journal:Human molecular genetics Jan 2007 , Vol 16 , pp. 36-49
Abstract:Nicotine dependence is one of the world's leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerström test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the beta3 nicotinic receptor subunit gene (P = 9.4 x 10(-5)). Biologically, the most compelling evidence for a risk variant came from a non-synonymous SNP in the alpha5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 x 10(-4)). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies.   PUBMED: 17135278
Ontological Annotations:
  • D005819: Genetic Markers (PubMed MeSH Annotations)
  • D006801: Humans (PubMed MeSH Annotations)
  • D009538: Nicotine (Publication, NCBO Annotator)
  • D016000: Cluster Analysis (PubMed MeSH Annotations)
  • D005838: Genotype (PubMed MeSH Annotations)
  • D014918: Wills (Publication, NCBO Annotator)
  • D012306: Risk (Publication, NCBO Annotator)
  • D012907: Smoking (Publication, NCBO Annotator)
  • D020641: Polymorphism, Single Nucleotide (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D001244: Association (Publication, NCBO Annotator)
  • D000368: Aged (PubMed MeSH Annotations)
  • D014029: Tobacco Use Disorder (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D000369: Aged, 80 and over (PubMed MeSH Annotations)
  • D014644: Genetic Variation (PubMed MeSH Annotations)
  • D002898: Chromosomes, Human, Pair 8 (PubMed MeSH Annotations)
  • D003643: Death (Publication, NCBO Annotator)
  • GO:0016265: death (Publication, NCBO Annotator)
  • D011978: Receptors, Nicotinic (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D000328: Adult (PubMed MeSH Annotations)
  • D008875: Middle Aged (PubMed MeSH Annotations)
  • D016022: Case-Control Studies (PubMed MeSH Annotations)

1 GeneSets from this Publication:

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Expand Tier III Human 33 Genes GS26305: Nicotine dependence Candidate Genes combined from GWAS and SNP association methods