Cigarette smoking is the single largest preventable source of morbidity and mortality in North America and Europe. Twin and adoption studies indicate that a majority of risk for nicotine dependence (ND) is genetic. A genome-wide association (WGA) study of cigarettes per day (CPD), as a quantitative trait, was conducted with ~ 7500 individuals of European origin. Genotyping was done with Affymetrix 500K chips. A SNP in the alpha 3 nicotinic receptor subunit gene (CHRNA3) was associated with CPD as a quantitative trait (p = 0.00007). Analyses of CPD in a case-control mode (cases defined as smoking >25 CPD versus controls <5 CPD), was done in a second European-origin population of ~ 6200 controls and ~ 1740 cases, genotyped at ~ 6000 SNPs. In this second population, a CHRNA3 SNP was strongly associated with CPD (p = 0.0000026, odds ratio 1.30, 95% CI 1.17-1.48). These results are similar to a case-control study of ND by Saccone et al (2007), who reported association of several CHRNA3 SNPs (0.0003
This research proposes to study DNA variations in genes which produce brain binding proteins for nicotine. These binding proteins are involved in the development of nicotine addiction. Understanding the function consequences of these DNA variations will provide direction in developing new medications for nicotine addiction.
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