In addition, BChE has a key role in the metabolism of various anesthetics, muscle relaxants and cocaine.78 Once absorbed, cocaine is rapidly transformed into two metabolites catalyzed by BChE, the enzyme produced by BCHE.79 BChE is synthesized primarily in the liver and is distributed throughout the intestinal mucosa, plasma and the brain.80 For these reasons, BChE has been conceptualized as a therapeutic agent for CoD.53 Researchers hypothesize that polymorphisms in BCHE lead to various enzyme profiles that allow different concentrations of cocaine to reach the reward system in the brain, thereby influencing susceptibility to developing addiction.81,82 As fast beta EEG has been associated with CoD in rodents83 and humans,84,85 the apparent links among BCHE, fast beta EEG and CoD should be explored further. Post hoc, we examined the association between 3q26 variants and fast beta EEG, adjusted for CoD. Results (Supplementary Figure S3B) show that the 3q26 association remains, although slightly diminished, suggesting that CoD is not driving the association among 3q26 and fast beta EEG in this sample. Also of potential relevance, variations within BCHE have also been implicated in association studies of learning and memory,86 cognitive functioning,87 schizophrenia88 and Alzheimer’s disease.89
