receptors have a role in nicotine-mediated analgesia, showing that reduced CHRNA4 expression in brain significantly attenuated sensitivity to nicotine agonist.68 This is consistent with our finding that rs2273500-C decreases CHRNA4 expression and, by lowering sensitivity to nicotine's effects, confers risk for nicotine dependence. Further supporting the relevance of CHRNA4, highly effective treatments for smoking cessation, varenicline69, 70 and cytisine,71 are partial agonists of α4β2 receptors. Interestingly, the item with the strongest rs2273500 association (latency to smoke in the morning) is the most robust of the FTND items in predicting smoking cessation12 and has been associated with both lung cancer72 and COPD.73
