Specific Aims:

The aims of this study are two-fold: 1. Identification of genes involved in nicotine dependence as measured by the FTND questionnaire; and 2 identification of genes involved in nicotine withdrawal as measured by the time to first cigarette (TFC), ascertained by the question "how soon do you smoke your first cigarette after you wake up in the morning".

Hypotheses:

If a trait is heritable, such as nicotine dependence, there must be gene(s) that influence the expression of the trait. Our hypothesis is, therefore, that since tobacco smoking and nicotine dependence have been demonstrated to be heritable, these traits must be influnced by some genes. Under this condition, if we collect a sufficient sample size, we should be able to detect some of those genes contributing to the traits by association analyses. To avoid selection bias, we plan to test all genes across the human genome.

Study Design:

We plan to use linear regression to analyze the association between genotypes and phenotypes. In the analyses, genotypes are treated as independent variables and pheotypes as dependent variables. Confounding variables, such as sex, age and population substructure will be used to exclude their effects. To maximize the coverage of the genome, genotype imputation will be performed to include all variants observed in the 1000 genomes project. The results from the ALSPAC sample will be combined with the results from other samples by meta-analysis.