Two approaches for addressing this problem have been applied in this study. One approach to address both the computational and statistical problem of the large number of tests is to filter the polymorphisms to be analyzed based on biological plausibility. In this case, we limited our analyses to polymorphisms located in or in linkage dis-equilibrium with nicotinic receptor subunit genes and filtered so that no two SNPs in our analysis had r2 > 0.95. Other filtering approaches could make use of additional biological information such as evolutionary conservation, biological pathways, and results from previous studies.
