Our candidate gene analyses identified an association (rs3027409, p<5.4×10−5) between genetic variation in MAOA and a dichotomized measure of smoking intensity (10 or less cigarettes smoked per day versus more than 10). This was the only gene-level result that remained significant after Bonferroni correction for the number of genes tested, which we regard as a conservative multiple-testing correction. This association is notable because of the role of the monoamine oxidases in the regulation of catecholamines and the inhibition of monoamine oxidases A and B by tobacco smoke [67]. There is substantial evidence that smoking results in reduced levels of the monoamine oxidase enzymes [67], [68] and subsequent reduced catabolism of dopamine likely contributes to the reinforcing and motivating effects of smoking. Investigation of MAO-related polymorphisms in relation to alcoholism [69], [70], Parkinson disease [71], [72], [73] and smoking [34], [67], [70], [74], [75], [76], [77] have yielded mixed results; our results suggest further investigation of this X-chromosome locus is warranted.
