Delayed reward discounting as an endophenotype for pathological gambling
Gray, Joshua Charles
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This study used an endophenotype approach to examine if delayed reward discounting (DRD; i.e., a behavioral economic index of impulsivity) clarifies associations between a panel of dopaminergic (DA) single nucleotide polymorphisms (SNPs) and pathological gambling (PG) in a sample of frequent gamblers of European ancestry (N = 175). In a priori tests, two loci previously associated with DRD (rs1800497 and rs4680) were not replicated, although significant associations were present in five genomically proximal loci. Exploratory analysis of 153 loci in genes related to DA neurotransmission revealed six additional significant associations, three in SLC18A2 and one in DRD5, DRD1, and DDC. Notably, an aggregate genetic risk score, generated from the 11 significantly associated SNPs, was significantly associated with PG severity and this relationship was fully mediated by their relation with DRD. This finding provides further evidence of genetic influences on DRD and preliminary support of DRD as an endophenotype for PG.