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Chunk #23 — Method — Genotyping and Imputation

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The interplay of genes and adolescent development in substance use disorders: leveraging findings from GWAS meta-analyses to test developmental hypotheses about nicotine consumption.
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SNPs used in the molecular genetic analysis were selected from supplemental materials reported in (Thorgeirsson, et al., 2010). Only SNPs in regions of interest were reported; that is, regions that harbored promising SNPS, including all genome-wide significant SNPs, based on the full meta-sample were reported. All SNPs with associations reported for cigarettes smoked per day were used in the present analysis. The SNP set was winnowed on the basis of linkage disequilibrium in an iterative fashion. The most significant SNP was selected, and all SNPs within r2 > .7 of that SNP were removed from the SNP set. Then the next most significant SNP in the reduced dataset was evaluated, and SNPs with r2 > .7 were removed, and so on. We chose a liberal r2 because our initial SNP set was rather small (602), and we wanted to exclude only the most highly-redundant SNPs. This process retained 92 of the 602 SNPs originally reported in the supplemental materials. For all analyses, these 92 SNPs were summed according to their meta-analytic regression weights to form a genetic risk score for tobacco use. The final 92 SNPs are listed in Supplemental Table 1.