Genetic influences on delay discounting in smokers: examination of a priori candidates and exploration of dopamine-related haplotypes

Abstract

Rationale: Delay discounting is a behavioral economic index of impulsivity that reflects a person's relative preference for small immediate rewards versus larger delayed rewards. Elevated delay discounting is robustly linked to addictive disorders and has been increasingly investigated as a viable endophenotype for genetic influences on addiction.

Objective: The aim of this study is to examine associations between delay discounting and two a priori loci, rs4680 in COMT and rs1800497 in ANKK1, and three exploratory haplotypes proximal to rs1800497 in a sample of daily smokers.

Methods: Participants were 713 (60.2 % male) daily smokers of European ancestry who completed a delay discounting assessment and provided a DNA sample.

Results: Significant associations were detected between greater discounting of medium magnitude rewards (~$55) and the G allele of rs4680, as well as the T allele of rs1800497. Exploratory haplotype analyses identified two haplotypes (rs1160467/rs1800497; rs6277/rs1079597) significantly associated with delay discounting rates. However, the rs1160467/rs1800497 haplotype associations appeared to be entirely attributable to variation in rs1800497, suggesting that the association of rs1800497 with discounting is best understood at the individual SNP level. Similarly, the rs6277/rs1079597 haplotype findings suggested that the association was specific to rs1079597.

Conclusions: This study provides further evidence that rs4680 and rs1800497 genotypes are significantly associated with delay discounting preferences and does so among smokers for the first time. The study also provides evidence of specificity for the rs1800497 association and identifies a novel locus, rs1079597, as a genetic contributor to higher delay discounting rates.

Figure 1

Linkage disequilibrium (LD) map among the proximal chromosome 11 loci. The loci are located in NCAM1 (rs618114), TTC12 (rs2303380, rs2282511), ANKK1 (rs877138, rs17115439, rs4938013, rs4938015, rs11604671, rs1800497), and DRD2 (rs6277, rs1079597).