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Chunk #14 — Results — Approach to Identify GO Terms and KEGG Pathways Affecting Cigarette Consumption

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Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways.
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We applied the ALIGATOR method independently to the OZALC-NAG study and the EA subjects from the SAGE study; analyzing the subset of SNPs that reached different significance levels (i.e., SNP p-value<0.001; 0.005; 0.01; and 0.05), to circumvent any bias introduced by this parameter [15]. We observed that for every combination of SNP p-value and category of gene enrichment p-value thresholds, there were a significant number of categories of genes enriched in common in the OZALC-NAG and SAGE studies (p-value<0.01) (Table 2). We selected the thresholds for the SNP and category of gene p-values (Table 2) that identified a significant excess of enriched categories of genes (p-value<0.05) for both studies. (See Table S1 panels A and B to see specific Gene Ontology and KEGG results respectively). We discarded those values for the SNP and category of gene threshold that were significant for only a single study: for example, although the OZALC-NAG study show a significant excess of pathways (p-value = 0.0346) with p-values lower than 0.005 when we analyzed the SNPs with p-values lower than 0.005, the SAGE study was not