Dopamine-Related Genotypes and Physical Activity Change During an Intervention: The Lifestyle Interventions and Independence for Elders Study

J Am Geriatr Soc. 2018 Jul;66(6):1172-1179. doi: 10.1111/jgs.15369. Epub 2018 Apr 10.


Objectives: To determine whether intervention-induced physical activity (PA) changes in sedentary older adults differed according to dopamine-related genotype.

Design: Randomized clinical trial (Lifestyle Interventions and Independence for Elders Trial (2010-13)).

Setting: Multicenter study, 8 U.S.

Participants: Volunteer sample of sedentary adults aged 70 to 89 at risk of disability (N=1635).

Interventions: Structured PA versus health education (HE) for an average of 2.6 years.

Measurements: Single-nucleotide polymorphisms of dopamine-related genes (dopamine receptor (DR) D1, DRD2, DRD3, and catechol-O-methyltransferase (COMT)) were assessed. Average moderate to vigorous PA (MVPA) was calculated using accelerometry (min/d) at baseline and 6, 12, and 24 months. Between-arm MVPA differences according to genotype and genotype with square root-transformed MVPA separately according to arm were tested, stratified according to race, and adjusted for multiple comparisons.

Results: White participants in the PA arm (n=513) had higher average square root transformed MVPA (4.91±1.91)than those in the HE arm (n=538) (4.51±1.82) (p=.001). Between-arm differences were greater for DRD2 Met/Met (high dopamine; HE: 4.76±1.80, PA: 5.53±1.60, p=.03) than Val/Val (low dopamine; HE: 4.58±1.92, PA: 4.81±1.83, p=.16); results were similar for COMT. In the PA arm, DRD2 Met/Met was associated with higher average MVPA (5.39±2.00) than Met/Val (4.46±2.51) (p=.01) and Val/Val (4.65±2.71) (p=.01). There were no associations for other genes. Associations were not significant in blacks but followed similar trends.

Conclusion: Higher dopamine signaling may support changes in PA during an intervention. The role of dopamine-related pathways in promoting PA participation and enhancing response to interventions in sedentary older adults should be studied.

Trial registration: Identifier: NCT01072500.

Keywords: aging; dopamine; physical activity; randomized controlled trial.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Accelerometry / methods
  • Aged
  • Catechol O-Methyltransferase / genetics*
  • Dopamine / metabolism*
  • Exercise Therapy* / methods
  • Exercise Therapy* / psychology
  • Exercise* / physiology
  • Exercise* / psychology
  • Female
  • Humans
  • Life Style / ethnology*
  • Male
  • Middle Aged
  • Mobility Limitation
  • Polymorphism, Single Nucleotide
  • Receptors, Dopamine D2 / genetics*
  • Risk Reduction Behavior
  • Sedentary Behavior / ethnology
  • Signal Transduction / genetics
  • Walking Speed / genetics*


  • DRD2 protein, human
  • Receptors, Dopamine D2
  • COMT protein, human
  • Catechol O-Methyltransferase
  • Dopamine

Associated data