Quantity-frequency data for smoking also provide evidence for a replicable “secondary” pharmacogenomic effect of moderate magnitude. Markers in the chromosome 15 gene cluster that encodes the α3, α5 and β4 nicotinic acetylcholine receptors display different allelic frequencies in heavy vs light smokers in each of several studies [3, 35, 69]. This chromosome 15 locus is likely to provide a good example of “secondary” pharmacogenomics, since it has not been associated as reproducibly with dependence on other substances.
