The role of SLC25A16 in stimulant dependence is unclear. This gene encodes a transporter of dephospho-coenzyme A (CoA) across the inner mitochondrial membrane50. Interestingly, kynureninase, the enzyme encoded by one of the other top-ranked loci in this study (KYNU), catalyzes the cleavage of kynurenine. Kynurenines may play a role in schizophrenia51 and one of the kynurenine metabolites, pantethine, is a precursor in the formation of CoA52, Thus, our genetic findings suggest a potential involvement of CoA metabolism in stimulant dependence. This idea is supported by a metabolomics study pointing to an increased energy demand caused by amphetamine and a commensurate increase in the number of fatty acids53. Fatty acid catabolism produces energy (adenosine triphosphate, ATP) by mitochondrial beta-oxidation yielding acetyl-CoA.
