the quantity smoked analysis. Excluding this gene cluster from the analysis showed that while the highly calcium permeable postsynaptic nicotinic acetylcholine receptors and the acetylcholine binding and downstream events pathways remained highly significant (i.e., P=1.27E-22 and P= 1.18E-21, respectively), the p-value for the presynaptic nicotinic acetylcholine receptors dropped to P=1.10E-04, suggesting that the association with this pathway was driven in part by the inclusion of these well-established candidate loci. Furthermore, quantity smoked was statistically associated with pathways regulating the immune system (with the cross presentation of soluble exogenous antigens endosomes pathway yielding the strongest association; P=4.38E-17), metabolism (where the regulation of ornithine decarboxylase ODC pathway yielded the strongest signal; P=6.71E-16), signal transduction (with the signaling by WNT pathway exceeding the significance threshold; P=1.18E-17) and asthma pathways (P=3.10E-04). Additionally, particularly enriched are the cell-cycle checkpoints pathways governing the transition of the new cell from one stage to another and the programmed cell-death, with strong association signals coming from the P53-dependent G1 DNA damage response pathway (P=7.24E-20) and from the pathway regulating apoptosis (P=1.84E-09).
