Dopamine D4 Receptor (DRD4) Box Score


Only recently has a specific genetic variant been associated with a human personality trait, Novelty Seeking. Since the first report in 1996, a number of studies have sought to replicate these first findings. This article summarizes the current status of the association between the dopamine D4 receptor (DRD4) gene and Novelty Seeking based on a recent meta‐analysis of almost four thousand subjects so far examined in molecular genetic studies.

Keywords: personality; genetics; dopamine D4 receptor; meta‐analysis; novelty Seeking

Figure 1.

Diagram of the DRD4 receptor with polymorphic sites (Paterson et al., ).

Figure 2.

Stem‐and‐leaf display of raw d values of the association between presence of long DRD4 allele and NS. This display shows all the raw data (d values). For example, the d value of Strobel et al. is 0.63 and is represented as 3 under the stem of 0.6, and the d value of Ebstein et al. is 0.58 and it is represented as 8 under the stem of 0.4 (that includes values between 0.40 and 0.59).



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

Benjamin J, Osher Y, Kotler M, et al. (2000) Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5‐HTTLPR) and catechol O‐methyltransferase (COMT). Molecular Psychiatry 5: 96–100.

Cloninger CR, Van Eerdewegh P, Goate A, et al. (1998) Anxiety proneness linked to epistatic loci in genome scan of human personality traits. American Journal of Medical Genetics 81: 313–317.

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

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Hunter JE and Schmidt FL (1990) Methods of Meta‐analysis: Correcting Error and Bias in Research Findings. Newbury Park: Sage Publications.

Ioannidis JP, Ntzani EE, Trikalinos TA and Contopoulos‐Ioannidis DG (2001) Replication validity of genetic association studies. Nature Genetics 29: 306–309.

Kluger AN, Siegfried Z and Ebstein RP (2002) A meta‐analysis of the association between DRD4 polymorphism and novelty seeking. Molecular Psychiatry 7: 712–717.

McCrae RR and Costa PT Jr (1997) Personality trait structure as a human universal. American Psychologist 52: 509–516.

Paterson AD, Sunohara GA and Kennedy JL (1999) Dopamine D4 receptor gene: novelty or nonsense? Neuropsychopharmacology 21: 3–16.

Strobel A, Wehr A, Michel A, Brocke B (1999) Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of Novelty seeking in a German population. Molecular Psychiatry 4: 378–384.

Tomitaka M, Tomitaka S, Otuka Y, et al., (1999) Association between novelty seeking and dopamine receptor D4 (DRD4) exon III polymorphism in Japanese subjects. American Journal of Medical Genetics 88(5): 469–471.

Further Reading

Benjamin J, Ebstein RP and Belmaker RH (2002) Molecular Genetics and the Human Personality, 1st edn Washington DC: American Psychiatric Publishing, Inc.

Cloninger CR (1987) A systematic method for clinical description and classification of personality variants. A proposal. Archives of General Psychiatry 44: 573–588.

Ding YC, Chi HC, Grady DL, et al. (2002) Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proceedings of the National Academy of Sciences of the United States of America 99: 309–314.

Egger M, Smith GD and Phillips AN (1997) Meta‐analysis: principles and procedures. British Medical Journal 315: 1533–1537.

Schork NJ, Fallin D, Thiel B, et al. (2001) The future of genetic case–control studies. Advances in Genetics 42: 191–212.

Zuckerman M (1994) Behavioral Expressions and Biosocial Bases of Sensation Seeking. New York, NY: Cambridge University Press.

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Ebstein, Richard P, Kluger, Avraham N, and Siegfried, Zahava(Jul 2006) Dopamine D4 Receptor (DRD4) Box Score. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005158]