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 bitter taste receptor TAS2R1, suspected to be able to sense the nicotine in cigarette smoke [36]. It has been shown that nicotine activates taste receptor pathways both specific for nicotine and also common to other bitter substances [37], [38]. This provides support for the finding that variants in some of the taste receptors can modulate cigarette consumption. Similarly, retinoic acid genes were also specific to the ALIGATOR analysis; but again it has been suggested that the activation of nicotinic receptors affects cellular signaling associated with retinoic acid target genes [39].
