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The dopaminergic reward system and leisure time exercise behavior: a candidate allele study.

ABSTRACT: PURPOSE:Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680) and three variable number of tandem repeats (VNTRs in DRD4, upstream of DRD5, and in DAT1) were investigated for an association with regular leisure time exercise behavior. MATERIALS AND METHODS:Data on exercise activities and at least one SNP/VNTR were available for 8,768 individuals aged 7 to 50 years old that were part of the Netherlands Twin Register. Exercise behavior was quantified as weekly metabolic equivalents of task (MET) spent on exercise activities. Mixed models were fitted in SPSS with genetic relatedness as a random effect. RESULTS:None of the genetic variants were associated with exercise behavior (P>.02), despite sufficient power to detect small effects. DISCUSSION AND CONCLUSIONS:We did not confirm that allelic variants involved in dopaminergic function play a role in creating individual differences in exercise behavior. A plea is made for large genome-wide association studies to unravel the genetic pathways that affect this health-enhancing behavior.

SUBMITTER: Huppertz C

PROVIDER: S-EPMC3964758 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The dopaminergic reward system and leisure time exercise behavior: a candidate allele study.

Huppertz Charlotte C Bartels Meike M Groen-Blokhuis Maria M MM Dolan Conor V CV de Moor Marleen H M MH Abdellaoui Abdel A van Beijsterveldt Catharina E M CE Ehli Erik A EA Hottenga Jouke-Jan JJ Willemsen Gonneke G Xiao Xiangjun X Scheet Paul P Davies Gareth E GE Boomsma Dorret I DI Hudziak James J JJ de Geus Eco J C EJ

BioMed research international 20140309

<h4>Purpose</h4>Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680) and three variable number of tandem repeats (VNTRs in DRD4, upstream of DRD5, an ...[more]

PMID: 24734235

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Project description:PurposeAlthough several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results.MethodsWe conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study.ResultsWe found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples.ConclusionsWe identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Project description:Abstract Objectives This study tested whether genotypes previously identified as moderators of other reinforcing behaviors, such as eating and drug abuse, also influence exercise reinforcement and the choice to exercise, measured as the reinforcing value of exercise relative to sedentary activities (screen time, reading, etc.). Linking specific genetic signatures of central mechanisms of reinforcement with an individual's exercise reinforcement has yet to be investigated and may uncover central mechanisms that underlie individual differences in exercise motivation, usual exercise behavior and long-term exercise adherence. Since preference and tolerance for exercise intensity influences exercise reinforcement, genetic contributions of these individual characteristics were also evaluated. Methods Men (n = 51) and women (n = 127) were measured for the reinforcing value of exercise relative to sedentary activities (RRVexercise), minutes of usual moderate-to-vigorous physical activity (MVPA), and completed the Preference for and Tolerance of the Intensity of Exercise Questionnaire. Participants provided a blood sample for genotyping of 23 SNPs previously identified to influence central dopamine release/uptake, reinforcement, or physical activity behaviors. ANOVA analysis determined differences in RRVexercise, preference, and tolerance among genotypes and linear regression analysis controlling for age, sex, and MVPA determined if genotype predicted RRVexercise, and preference/tolerance for exercise intensity. Results Having at least one copy of the G allele for the DRD2/ANKK1 polymorphism (rs1800497) confers greater RRVexercise by increasing receptor binding or expression of the dopamine D2 receptor. Greater tolerance for exercise intensity was observed among those homozygous for the T allele for the CNR1 polymorphism (rs6454672), had at least one copy of the G allele for the GABRG3 polymorphism (rs8036270) and had at least one copy of the T allele for the LPR polymorphism (rs12405556) by influencing pain neurotransmission and leptin receptor binding. Conclusions Similar to other reinforcing behaviors, there is a genetic contribution to exercise reinforcement and tolerance for exercise intensity. Funding Sources USDA, Agricultural Research Service, Project 3062-51000-051-00D.

Project description:PurposeIt has been suggested that reward system dysfunction may account for emotion and pain suffering in migraine. However, there is a lack of evidence whether the altered reward system connectivity is directly associated with clinical manifestations, including negative affect and ictal pain severity and, at the molecular level, the dopamine (DA) D2/D3 receptors (D2/3Rs) signaling implicated in encoding motivational and emotional cues.Patients and methodsWe acquired resting-state functional MRI from interictal episodic migraine (EM) patients and age-matched healthy controls, as well as positron emission tomography (PET) with [11C]raclopride, a selective radiotracer for DA D2/3Rs, from a subset of these participants. The nucleus accumbens (NAc) was seeded to measure functional connectivity (FC) and DA D2/3Rs availability based on its essential involvement in pain-related aversive/reward functions. Associations of the brain measures with positive/negative affect and ictal pain severity were also assessed.ResultsCompared with controls, the EM group showed weaker right NAc connectivity with areas implicated in pain and emotional regulation, such as the amygdala, rostral anterior cingulate cortex, hippocampus, and thalamus; but showed stronger left NAc connectivity with the dorsolateral prefrontal cortex and lingual gyrus. Moreover, among the altered NAc connectivities, only right NAc-amygdala connectivity was inversely correlated with DA D2/3Rs availability in migraine patients (diagnostic group-by-D2/3Rs interaction p < 0.007). At a clinical level, such weaker NAc-amygdala connectivity was associated with lower interictal positive affect and greater ictal pain severity over the head and facial extension area (pain area and intensity number summation, PAINS).ConclusionTogether, our findings suggest that altered reward system connectivity, specifically between the NAc and amygdala, might be affected by endogenous DA D2/3Rs signaling, and such process might be a neural mechanism that underlies emotional and pain suffering in episodic migraineurs.

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The dopaminergic reward system and leisure time exercise behavior: a candidate allele study.

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The dopaminergic reward system and leisure time exercise behavior: a candidate allele study.

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