Publication Details

Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs.

Authors:Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE
Title:Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs.
Journal:BMC genetics Apr 2007 , Vol 8 , pp. 10
Abstract:BACKGROUND: Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. RESULTS: These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms (SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p < 0.00001). CONCLUSION: These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers with the treatments that are most likely to benefit them.   PUBMED: 17407593
Ontological Annotations:
  • D011506: Proteins (Publication, NCBO Annotator)
  • D032882: Comprehension (Publication, NCBO Annotator)
  • D002448: Cell Adhesion (Publication, NCBO Annotator)
  • D006801: Humans (PubMed MeSH Annotations)
  • D012907: Smoking (Publication, NCBO Annotator)
  • D020641: Polymorphism, Single Nucleotide (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D014029: Tobacco Use Disorder (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D013375: Substance Withdrawal Syndrome (PubMed MeSH Annotations)
  • D001076: Aptitude (Publication, NCBO Annotator)
  • D004247: DNA (Publication, NCBO Annotator)
  • D008967: Molecular Biology (Publication, NCBO Annotator)
  • D002477: Cells (Publication, NCBO Annotator)
  • D000328: Adult (PubMed MeSH Annotations)
  • D020022: Genetic Predisposition to Disease (PubMed MeSH Annotations)
  • D012926: Social Control, Formal (Publication, NCBO Annotator)
  • D005787: Gene Frequency (Publication, NCBO Annotator)
  • D004798: Enzymes (Publication, NCBO Annotator)
  • GO:0005623: cell (Publication, NCBO Annotator)
  • D018377: Neurotransmitter Agents (Publication, NCBO Annotator)
  • D055106: Genome-Wide Association Study (Publication, NCBO Annotator)
  • D012718: Set (Psychology) (Publication, NCBO Annotator)
  • D058028: Research Report (Publication, NCBO Annotator)
  • D001244: Association (Publication, NCBO Annotator)
  • D035061: Control Groups (Publication, NCBO Annotator)
  • D012313: RNA (Publication, NCBO Annotator)
  • D005823: Genetics (Publication, NCBO Annotator)
  • D015894: Genome, Human (PubMed MeSH Annotations)
  • D000483: Alleles (Publication, NCBO Annotator)
  • GO:0007155: cell adhesion (Publication, NCBO Annotator)
  • D005838: Genotype (Publication, NCBO Annotator)
  • D016540: Smoking Cessation (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D005819: Genetic Markers (PubMed MeSH Annotations)
  • D009538: Nicotine (Publication, NCBO Annotator)
  • D013812: Therapeutics (Publication, NCBO Annotator)

2 GeneSets from this Publication:

Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier III Human 19 Genes GS14905: Genes implicated in nicotine dependence
Expand Tier III Human 43 Genes GS14906: Genes implicated in smoking cessation