Dopaminergic Genetic Variants and Voluntary Externally Paced Exercise Behavior

Purpose Most candidate gene studies on the neurobiology of voluntary exercise behavior have focused on the dopaminergic signaling pathway and its role in the mesolimbic reward system. We hypothesized that dopaminergic candidate genes may influence exercise behavior through additional effects on executive functioning and that these effects are only detected when the types of exercise activity are taken into account. Methods Data on voluntary exercise behavior and at least one single-nucleotide polymorphism/variable number of tandem repeat (VNTR) were available for 12,929 participants of the Netherlands Twin Registry. Exercise activity was classified as externally paced if a high level of executive function skill was required. The total volume of voluntary exercise (minutes per week) as well as the volume specifically spent on externally paced activities were tested for association with nine functional dopaminergic polymorphisms (DRD1: rs265981, DRD2/ANKK1: rs1800497, DRD3: rs6280, DRD4: VNTR 48 bp, DRD5: VNTR 130–166 bp, DBH: rs2519152, DAT1: VNTR 40 bp, COMT: rs4680, MAOA: VNTR 30 bp), a polygenic score (PGS) based on nine alleles leading to lower dopamine responsiveness, and a PGS based on three alleles associated with both higher reward sensitivity and better executive functioning (DRD2/ANKK1: "G" allele, COMT: Met allele, DAT1: 440-bp allele). Results No association with total exercise volume or externally paced exercise volume was found for individual alleles or the nine-allele PGS. The volume of externally paced exercise behavior was significantly associated with the reward and executive function congruent PGS. This association was driven by the DAT1 440-bp and COMT Met allele, which acted as increaser alleles for externally paced exercise behavior. Conclusions Taking into account the types of exercise activity may increase the success of identifying genetic variants and unraveling the neurobiology of voluntary exercise behavior.

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