Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking

Twin and adoption studies suggest that 30 to 60% of the variance in many personality traits is due to inherited factors. However, there is little knowledge of the number or identity of the responsible genes, how they differ between individuals, or how their gene products interact with the developing brain and with environmental and experiential factors to generate the complex blend of attitudes and actions that comprise human temperament1. In the accompanying paper, Ebstein et al.2 have found a population association between a long allele of polymorphic exon III repeat sequence of the D4 dopamine receptor gene (DADR) and the normal personality trait of Novelty Seeking. The possibility of a causal relationship between DADR and Novelty Seeking is further supported by studies showing that the number of exon III repeats can affect the binding of ligands to the receptor3,4; that DADR is expressed in lim-bic areas involved in cognition and emotion5,6; that dopamine mediates exploratory behaviour in experimental animals7–12; that the rewarding effects of amphetamines and cocaine are related to dopamine release13; and that Novelty Seeking is low in dopamine-deficient patients with Parkinson's disease14. We investigated the relationship between DADR exon III sequence variants and personality test scores in a population of 315 mostly male siblings, other family members and individuals from the United States. The association between long alleles of exon III and personality traits related to Novelty Seeking was confirmed. Moreover, family studies showed that this association is the result of genetic transmission rather than of population stratification.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Bouchard, T.J.J., Genes, environment, and personality. Science 264, 1700–1701 (1994).

    Article  Google Scholar 

  2. 2

    Ebstein, R.R. et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nature Genet. 12, 78–80 (1996).

    CAS  Article  Google Scholar 

  3. 3

    Van Tol, H.H.M. et al. Multiple dopamine D4 receptor variants in the human population. Nature 358, 149–152 (1992).

    CAS  Article  Google Scholar 

  4. 4

    Asghari, V. et al. Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. Mol. Pharmacol. 46, 364–373 (1994).

    CAS  PubMed  Google Scholar 

  5. 5

    Van Tol, H.H.M. et al. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350, 610–614 (1991).

    CAS  Article  Google Scholar 

  6. 6

    Meador-Woodruff, J.H. et al. Dopamine receptor gene expression in the human medial temporal lobe. Neuropsychopharmacology. 10, 239–248 (1994).

    CAS  Article  Google Scholar 

  7. 7

    Stellar, J.R. & Stellar, E. in The Neurobiology of Motivation and Reward (Springer-Verlag, New York, 1985).

    Google Scholar 

  8. 8

    Kalivas, R.W. & Nemeroff, C.B. in The Mesocorticolimbic Dopamine System 537(Annals of the New York Academy of Sciences, New York, 1988).

    Google Scholar 

  9. 9

    Hooks, M.S. & Kalivas, R.W. Involvement of dopamine and excitatory amino acid transmission in novelty-induced motor activity. J. Pharmacol. Exp. Ther. 269, 976–988 (1994).

    CAS  PubMed  Google Scholar 

  10. 10

    Fink, J.S. & Reis, D.J. Genetic variations in midbrain dopamine cell number: parallel with differences in responses to dopaminergic agonists and in naturalistic behaviors mediated by central dopaminergic systems. Brain Res. 222, 335–349 (1981).

    CAS  Article  Google Scholar 

  11. 11

    Fink, J.S. & Smith, G.P. Mesolimbic and mesocortical dopaminergic neurons are necessary for normal exploratory behavior in rats. Neurosci. Lett. 17, 61–65 (1980).

    CAS  Article  Google Scholar 

  12. 12

    Cloninger, C.R., Przybeck, T.R. & Svrakic, D.M. The Tridimensional Personality Questionnaire: U.S. normative data. Psychol. Rep. 69, 1047–1057 (1991).

    CAS  Article  Google Scholar 

  13. 13

    Ritz, M.C. & Kuhar, M.J. Psychostimulant drugs and a dopamine hypothesis regarding addiction: update on recent research. Biochem. Soc. Symp. 59, 51–64 (1993).

    CAS  PubMed  Google Scholar 

  14. 14

    Menza, M.A., Golbe, L.I., Cody, R.A. & Forman, N.E. Dopamine-related personality traits in Parkinsons disease. Neurology 43, 505–508 (1993).

    CAS  Article  Google Scholar 

  15. 15

    Cloninger, C.R. A systematic method for clinical description and classification of personality variants. A proposal. Arch. Gen. Psych. 44, 573–588 (1987).

    CAS  Article  Google Scholar 

  16. 16

    Costa, R.T.J. & McCrae, R.R. . in Revised NEO Personality Inventory (NEO PI-R) and NEO Five Inventory (NEO-FFI) professional manual (Psychological Assessment Resources, Odessa, FL, 1992).

    Google Scholar 

  17. 17

    McCrae, R.R. & Costa, P.T.J. in Personality in Adulthood (Guilford, New York, 1990).

    Google Scholar 

  18. 18

    Costa, P.T.J. & McCrae, R.R. in The Revised NEO Personality Inventory (NEO PI-R) (eds Cheek, J. & Donahue, E.M.) (Plenum, New York, In press).

  19. 19

    Lichter, J.B. et al. A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum. Mol. Genet. 2, 767–773 (1993).

    CAS  Article  Google Scholar 

  20. 20

    George, V.T. & Elston, R.C. Testing the association between polymorphic markers and quantitative traits in pedigrees. Genet. Epidemiol. 4, 193–201 (1987).

    CAS  Article  Google Scholar 

  21. 21

    Nick, T.G., George, V., Elston, R.C. & Wilson, A.F. Statistical validity for testing associations between genetic markers and quantitative traits in family data. Genet. Epidemiol. 12, 145–146 (1995).

    CAS  Article  Google Scholar 

  22. 22

    Elston, R.C., George, V.T. & Sorant, A.J.M. in Trait-marker association program (ASSOC). In S.A.G.E. Users Guide, Release 2.2 (Department of Biometry and Genetics (LSU Medical Center, New Orleans, 1994).

  23. 23

    Spielman, R.S., McGinnis, R.E. & Ewens, W.J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506–516 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Cohen, J. in Statistical Power Analysis for the Behavioral Sciences (Erlbaum,Hillsdale,NJ, 1988).

    Google Scholar 

  25. 25

    Heath, A.C., Cloninger, C.R. & Martin, N.G. Testing a model for thegenetic structure of personality: a comparison of the personality systems of Cloninger and Eysenck. J. Pers. Soc. Psychol. 66, 762–775 (1994).

    CAS  Article  Google Scholar 

  26. 26

    Plomin, R., Owen, M.J. & McGuffin, P. The genetic basis of complex human behaviors. Science 264, 1733–1739 (1994).

    CAS  Article  Google Scholar 

  27. 27

    Lander, E.S. & Schork, N.J. Genetic dissection of complex traits. Science 265, 2037–2048 (1994).

    CAS  Article  Google Scholar 

  28. 28

    Hamer, D.H. & Copeland, P. in The Science of Desire (Simon & Schuester, New York, 1994).

    Google Scholar 

  29. 29

    Costa, P.T.J. & McCrae, R.R. in The Developing Structure of Temperament and Personality from Infancy to Adulthood (eds. Halverson, C.F., Kohnstamm, G.A. & Martin, R.R) 139–150 (Lawrence Erlbaum Associates, Hillsdale, NJ, in the press).

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Benjamin, J., Li, L., Patterson, C. et al. Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat Genet 12, 81–84 (1996).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing