Publication Details

Novel genes identified in a high-density genome wide association study for nicotine dependence.

Authors:Bierut LJ, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau OF, Swan GE, Rutter J, Bertelsen S, Fox L, Fugman D, Goate AM, Hinrichs AL, Konvicka K, Martin NG, Montgomery GW, Saccone NL, Saccone SF, Wang JC, Chase GA, Rice JP, Ballinger DG
Title:Novel genes identified in a high-density genome wide association study for nicotine dependence.
Journal:Human molecular genetics Jan 2007 , Vol 16 , pp. 24-35
Abstract:Tobacco use is a leading contributor to disability and death worldwide, and genetic factors contribute in part to the development of nicotine dependence. To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers as cases and non-dependent smokers as controls. To allow the efficient, rapid, and cost effective screen of the genome, the study was carried out using a two-stage design. In the first stage, genotyping of over 2.4 million single nucleotide polymorphisms (SNPs) was completed in case and control pools. In the second stage, we selected SNPs for individual genotyping based on the most significant allele frequency differences between cases and controls from the pooled results. Individual genotyping was performed in 1050 cases and 879 controls using 31 960 selected SNPs. The primary analysis, a logistic regression model with covariates of age, gender, genotype and gender by genotype interaction, identified 35 SNPs with P-values less than 10(-4) (minimum P-value 1.53 x 10(-6)). Although none of the individual findings is statistically significant after correcting for multiple tests, additional statistical analyses support the existence of true findings in this group. Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor. This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community.   PUBMED: 17158188
Ontological Annotations:
  • D014026: Tobacco (Publication, NCBO Annotator)
  • D005838: Genotype (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D012111: Residence Characteristics (Publication, NCBO Annotator)
  • D009538: Nicotine (Publication, NCBO Annotator)
  • D006801: Humans (PubMed MeSH Annotations)
  • D005783: Gender Identity (Publication, NCBO Annotator)
  • D005544: Forecasting (Publication, NCBO Annotator)
  • D014937: Work (Publication, NCBO Annotator)
  • D003365: Costs and Cost Analysis (Publication, NCBO Annotator)
  • D020641: Polymorphism, Single Nucleotide (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D014029: Tobacco Use Disorder (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D012043: Regression (Psychology) (Publication, NCBO Annotator)
  • D003643: Death (Publication, NCBO Annotator)
  • GO:0016265: death (Publication, NCBO Annotator)
  • D012907: Smoking (PubMed MeSH Annotations)
  • D015894: Genome, Human (PubMed MeSH Annotations)
  • D000483: Alleles (Publication, NCBO Annotator)
  • D005787: Gene Frequency (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D020022: Genetic Predisposition to Disease (PubMed MeSH Annotations)
  • D055106: Genome-Wide Association Study (Publication, NCBO Annotator)
  • D016022: Case-Control Studies (PubMed MeSH Annotations)
  • D016015: Logistic Models (Publication, NCBO Annotator)
  • D001244: Association (Publication, NCBO Annotator)

1 GeneSets from this Publication:

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Expand Tier III Human 14 Genes GS26287: Positional candidates from genome-wide association study for nicotine dependence