While twin and family studies were able to establish that cigarette use phenotypes were heritable, technological advances made it possible to sequence the human genome and look for the genes underlying these twin and family heritability estimates. Gene finding methods are used to determine the locations of gene variants that differentially impact the liability to traits. In general, these gene-finding methods are statistical in nature, such that researchers infer the probability that a locus in the genomic region under investigation contributes to liability for the trait (e.g. cigarette use phenotypes) from an examination of the distribution of genetic markers within either families, as in linkage studies, or populations, as in genome-wide association studies (GWAS) (23). Genome-wide linkage studies were first used to identify chromosomal regions that could have contained loci contributing to cigarette use phenotypes, involved with either the neurotransmission of neuromodulators or the rewarding efforts of nicotine on the mesolimbic system (24). Candidate gene studies investigated associations between measures of cigarette use initiation, intensity, and dependence and genes involved with nicotine receptors, dopaminergic transmission, and serotonin transporters. Despite some
