Alpha-5/alpha-3 Nicotinic Receptor Subunit Alleles Increase Risk for Heavy Smoking

Mol Psychiatry. 2008 Apr;13(4):368-73. doi: 10.1038/sj.mp.4002154. Epub 2008 Jan 29.

Abstract

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Chromosomes, Human, Pair 15 / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Microarray Analysis / methods
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Nicotinic / genetics*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tobacco Use Disorder / epidemiology
  • Tobacco Use Disorder / genetics*

Substances

  • CHRNA5 protein, human
  • Nerve Tissue Proteins
  • Receptors, Nicotinic
  • nicotinic receptor subunit alpha3