at least partially drive that propensity. FTO has also been associated with addictive behaviors. Although initially identified as a regulator of eating and obesity traits [56, 57], though probably not through an effect of FTO itself but rather as a consequence of variants in the gene that affect expression of IRX3 and IRX5 [56, 58]. FTO has also been associated with alcohol dependence [46-48] and connectivity in a dopamine-dependent reward circuit of meso-striato-prefrontal regions of the human brain [59]. PTPRZ1 binds to two neurotrophic cytokines [pleiotrophin (PTN) and midkine (MK)] that, along with other functions, contribute to the extinction of cocaine and amphetamine-seeking behaviors [49, 50] and limit morphine withdrawal syndrome [60]. The variants we identified, however, were ~100 KB away from the gene and may not strongly suggest a role for this gene in SUD risk. The top gene identified through gene based tests, CACNA1B in EAs for CD TD, encodes a pore-forming subunit of the presynaptic neuronal voltage-dependent calcium channel. Genes from this family of neuronal regulators of calcium and potassium levels were associated with their respective traits in our previous OD and CD GWAS papers [13, 18]. This, along with the fact that the membrane polarization gene
