We first focused on the first of the two research questions: 1) smokers vs nonsmokers, with a special interest in the genes that have overlap with dependence on other substances. When we compare allele frequencies in 134 nicotine-dependent vs 320 control individuals, 88,937 of the 520,000 tested SNPs displayed t values that provide nominally-significant abuser vs control allele frequency differences at p < 0.005. These nominally-positive SNPs are positioned near clustered-positive SNPs from four other abuser-control comparisons to extents that are greater than expected by chance (Table 1). 4701 of these nominally-significant SNPs lie within 100 Kb of a cluster of nominally-positive SNPs from replicate African-American and European-American NIDA polysubstance abuser vs control comparisons. Monte Carlo p values for this convergence were 0.0002. Thus, only 2 of 10,000 Monte Carlo simulation trials that each began by selecting 88,937 random SNPs displayed so many nominally-significant results near the clustered positive results from the two NIDA samples. 2133 of the nominally-significant SNPs from the current nicotine dependent vs control comparison meet several criteria. They 1) lie near clusters of positive SNPs from
