Journal home
Advance online publication
Current issue
Archive
Press releases
Free Association (blog)
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Biotechnology
Nature Cell Biology
Nature Medicine
Nature Methods
Nature Reviews Cancer
Nature Reviews Genetics
Nature Reviews Molecular Cell Biology
news@nature.com
Nature Conferences
RNAi Gateway
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
Letter
Nature Genetics  12, 78 - 80 (1996)
doi:10.1038/ng0196-78

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

Richard P. Ebstein1, 3, 4, Olga Novick2, Roberto Umansky2, Beatrice Priel2, Yamima Osher2, Darren Blaine1, Estelle R. Bennett1, Lubov Nemanov1, Miri Katz1 & Robert H. Belmaker2

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

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

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

  4Correspondence should be addressed to R.P.E.

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.

REFERENCES
  1. Plomin, R., Owen, M.J. & McGuffin, P. The genetic basis of complex human behaviors. Science. 264, 733−1739 (1994).
  2. Cloninger, C.R., Svrakic, D.M. & Przybeck, T.R. A psychobiological model of temperament and character. Arch. Gen. Psych. 50, 975−990 (1993).
  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).
  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).
  5. Van Tol, H.H.M et al. .Multiple dopamine D4 receptor variants in the human population. Nature. 358, 149−152 (1992).
  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).
  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).
  8. Seeman, P. & Van Tol, H.H.M. Dopamine receptor pharmacology. Trends Pharmacol. Sci. 15, 264−270 (1994).
  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).
  10. Owen, M.J. & McGuffin, P. Association and linkage: complementary strategies for complex disorders. J. Med. Gen. 30, 638−639 (1993).
  11. Lander, E.S. & Schork, N.J. Genetic dissection of complex traits. Science. 265, 2037−2048 (1994).
  12. Thomsom, G. Identifying complex disease genes: progress and paradigms. Nature Genet. 8, 108−110 (1994).
  13. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241−247 (1995).
  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).
  15. van Bockxmeer, F.M. ApoE and ACE genes: impact on human longevity. Nature Genet. 6, 4−5 (1994).
  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).
  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).
  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).
  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).
  20. Krontirls, T.G. Minisatellites and human disease. Science. 269, 1682−1683 (1995).
 Top
 Top
References
Previous | Next
Table of contents
Download PDFDownload PDF
Send to a friendSend to a friend
Save this linkSave this link

natureevents

References
Export citation
Export references
natureproducts

Search buyers guide:

 
ADVERTISEMENT
 
Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | Permissions | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | naturereprints | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©1996 Nature Publishing Group | Privacy policy