Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression

PLoS One. 2014 May 16;9(5):e93772. doi: 10.1371/journal.pone.0093772. eCollection 2014.


Background: Depression is a common source of human disability for which etiologic insights remain limited. Although abnormalities of monoamine neurotransmission, including dopamine, are theorized to contribute to the pathophysiology of depression, evidence linking dopamine-related genes to depression has been mixed. The current study sought to address this knowledge-gap by examining whether the combined effect of dopamine polymorphisms was associated with depressive symptomatology in both healthy individuals and individuals with depression.

Methods: Data were drawn from three independent samples: (1) a discovery sample of healthy adult participants (n = 273); (2) a replication sample of adults with depression (n = 1,267); and (3) a replication sample of healthy adult participants (n = 382). A genetic risk score was created by combining functional polymorphisms from five genes involved in synaptic dopamine availability (COMT and DAT) and dopamine receptor binding (DRD1, DRD2, DRD3).

Results: In the discovery sample, the genetic risk score was associated with depressive symptomatology (β = -0.80, p = 0.003), with lower dopamine genetic risk scores (indicating lower dopaminergic neurotransmission) predicting higher levels of depression. This result was replicated with a similar genetic risk score based on imputed genetic data from adults with depression (β = -0.51, p = 0.04). Results were of similar magnitude and in the expected direction in a cohort of healthy adult participants (β = -0.86, p = 0.15).

Conclusions: Sequence variation in multiple genes regulating dopamine neurotransmission may influence depressive symptoms, in a manner that appears to be additive. Further studies are required to confirm the role of genetic variation in dopamine metabolism and depression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Catechol O-Methyltransferase / genetics*
  • Depression / genetics*
  • Depression / pathology
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Genetic Variation*
  • Genotype
  • Humans
  • Linear Models
  • Phenotype*
  • Receptors, Dopamine / genetics*
  • Risk Assessment / methods*


  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine
  • COMT protein, human
  • Catechol O-Methyltransferase