Skip to main content

Thank you for visiting nature.com. 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.

  • Letter
  • Published:

Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking

Nature Genetics volume 12, pages 78–80 (1996)Cite this article

Human personality traits which can be reliably measured by any of a number of rating scales, show a considerable heritable component1,2. The tridimensional personality questionnaire (TPQ) is one such instrument and was designed by Cloninger to measure four distinct domains of temperament — Novelty Seeking, Harm Avoidance, Reward Dependence and Persistence — that are hypothesized to be based on distinct neurochemical and genetic substrates. Cloninger proposed that individual variations in the Novelty Seeking trait are mediated by genetic variability in dopamine transmission2. Individuals who score higher than average on the TPQ Novelty Seeking scale are characterized as impulsive, exploratory, fickle, excitable, quick-tempered and extravagant, whereas those who score lower than average tend to be reflective, rigid, loyal, stoic, slow-tempered and frugal. We now show that higher than average Novelty Seeking test scores in a group of 124 unrelated Israeli subjects are significantly associated with a particular exonic polymorphism, the 7 repeat allele in the locus for the D4 dopamine receptor gene (D4DR). The association of high Novelty Seeking and the 7-repeat allele was independent of ethnicity, sex or age of the subjects. This work, together with the accompanying confirmations in this issue3, provides the first replicated association between a specific genetic locus involved in neuro-transmission and a normal personality trait.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Plomin, R., Owen, M.J. & McGuffin, P. The genetic basis of complex human behaviors. Science. 264, 733–1739 (1994).

    Article  Google Scholar 

  2. Cloninger, C.R., Svrakic, D.M. & Przybeck, T.R. A psychobiological model of temperament and character. Arch. Gen. Psych. 50, 975–990 (1993).

    Article  CAS  Google Scholar 

  3. Benjamin, J., Greenberg, B., Murphy, D.L., Lin, L., Patterson, C. & Hamer, D.H. Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nature Genet. 12, 81–84 (1996).

    Article  CAS  Google Scholar 

  4. Lichter, J.B., Barr, C.L., Kennedy, J.L., Van Tol, H.H.M, Kidd, K.K. & Livak, K.J. A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum. Molec. Genet. 2, 767–773 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  7. 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).

    Article  CAS  Google Scholar 

  8. Seeman, P. & Van Tol, H.H.M. Dopamine receptor pharmacology. Trends Pharmacol. Sci. 15, 264–270 (1994).

    Article  CAS  Google Scholar 

  9. Green, S.A., Turki, J., Innis, M. & Liggett, S.B. Amino-terminal polymorphisms of the human beta2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 33, 9414–9419 (1994).

    Article  CAS  Google Scholar 

  10. Owen, M.J. & McGuffin, P. Association and linkage: complementary strategies for complex disorders. J. Med. Gen. 30, 638–639 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Thomsom, G. Identifying complex disease genes: progress and paradigms. Nature Genet. 8, 108–110 (1994).

    Article  Google Scholar 

  13. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

    Article  CAS  Google Scholar 

  14. Cambien, F. et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 359, 641–644 (1992).

    Article  CAS  Google Scholar 

  15. van Bockxmeer, F.M. ApoE and ACE genes: impact on human longevity. Nature Genet. 6, 4–5 (1994).

    Article  CAS  Google Scholar 

  16. Corder, E.H. et al. Protective effect of apolipoprotein E type 2 allele for late ons.et Al zheimer disease. Nature Genet. 7, 180–184 (1994).

    Google Scholar 

  17. Sommer, S.S., Lind, T.J., Heston, L.L. & Sobell, J.L. Dopamine D4 receptor variants in unrelated schizophrenic cases and controls. Am. J. Med. Gen. 48, 90–93 (1993).

    Article  CAS  Google Scholar 

  18. Macciardi, F. et al. Analysis of the D4 dopamine receptor gene variant in an Italian schizophrenic kindred. Arch. Gen. Psych. 51, 288–292 (1994).

    Article  CAS  Google Scholar 

  19. Vanyukov, M.M., Moss, H.B., Yu, L.M., Tarter, R.E., Ranjan, D. Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early oneset alcoholism/substance abuse. Am. J. Med. Genet. (Neuropsychiatric Genet.) 60, 122–126 (1995).

    Article  CAS  Google Scholar 

  20. Krontirls, T.G. Minisatellites and human disease. Science. 269, 1682–1683 (1995).

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Richard P. Ebstein: Correspondence should be addressed to R.P.E.

Authors and Affiliations

  1. Research Laboratory, S. Herzog Memorial Hospital, P.O.Box 35300, Jerusalem, 91351, Israel

    Richard P. Ebstein, Darren Blaine, Estelle R. Bennett, Lubov Nemanov & Miri Katz

  2. Beersheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.Box 4600, Beersheva, Israel

    Olga Novick, Roberto Umansky, Beatrice Priel, Yamima Osher & Robert H. Belmaker

  3. Laboratory Director, S. Herzog Memorial Hospital, P.O.Box 35300, Jerusalem, 91351, Israel

    Richard P. Ebstein

Authors
  1. Richard P. Ebstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga Novick
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberto Umansky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beatrice Priel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yamima Osher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Darren Blaine
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Estelle R. Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lubov Nemanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Miri Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Robert H. Belmaker
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ebstein, R., Novick, O., Umansky, R. et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 12, 78–80 (1996). https://doi.org/10.1038/ng0196-78

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0196-78

Search

Advanced search

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
pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy