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Chunk #30 — Discussion

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Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways.
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We did not restrict our analysis to the ALIGATOR method, but also applied the MAGENTA method, as each of these methods can provide complementary findings [35]. Only the GO terms for cholinergic receptors were consistently significant in the OZALC-NAG, SAGE and ARIC studies using the MAGENTA method, increasing the levels of certainty of the original ALIGATOR predictions. In contrast, the ALIGATOR method identified other GO terms and KEGG pathways common to the three datasets. We verified if the assumption of one causal gene per signal made by the MAGENTA method caused the different results. However, correcting or not for physically proximal genes did not change substantially the MAGENTA results for these categories of genes. It could be argued that ALIGATOR results are a product of the specificity of the method, and are not susceptibility factors for smoking. However, some of the genes included in these significant GO terms were previously reported to influence smoking behaviors, which increases the confidence in these findings (e.g., GRM8 [32] and GRM7 [31], [30]). Our analysis detected other genes common to all datasets, including the