Another investigation of this polymorphism in iPSC-derived dopaminergic neurons demonstrated that Asn-398 variant has a decreased sensitivity to the receptor agonists (Deflorio et al., 2017). However, increases in current in response to agonists were observed (Deflorio et al., 2017), consistent with findings in glutamatergic but not dopaminergic neurons by Oni et al., 2016. The difference in findings of the variants’ effects on receptor function by neuron type between these studies could be attributed to differences in iPSC differentiation protocols. While these studies elucidate functional consequences of a GWAS variant, they also highlight the need for replication and standardization of differentiation protocols.
