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A meta-analysis of the association between DRD4 polymorphism and novelty seeking

Abstract

A meta-analytical review of 20 studies (n = 3907) of the association between DRD4 polymorphism and novelty seeking suggests the following conclusions: (a) on average, there is no association between DRD4 polymorphism and novelty seeking (average d= 0.06 with 95% CI of ± 0.09), where 13 reports suggest that the presence of longer alleles is associated with higher novelty seeking scores and seven reports suggest the opposite; (b) there is a true heterogeneity among the studies (ie, unknown moderators do exist) but the strength of the association between DRD4 polymorphism and novelty seeking in the presence of any (unknown) moderator is likely to be weak; (c) search for moderators has not yielded any reliable explanation for the variability among studies. We propose that to find such moderators, theory-driven research for potential interaction, coupled with larger sample sizes should be employed. The growing availability of powerful statistical techniques, high-throughput genotyping and large numbers of polymorphic markers such as single nucleotide polymorphisms makes such proposed studies increasingly feasible.

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References

  1. Loehlin JC . Genes and Environment in Personality Development Sage Publications: Newbury Park 1992

    Google Scholar 

  2. Cloninger CR . A systematic method for clinical description and classification of personality variants: a proposal Arch Gen Psychiatry 1987; 44: 573–588

    Article  CAS  Google Scholar 

  3. Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O et al. Multiple dopamine D4 receptor variants in the human population Nature 1992; 358: 149–152

    Article  CAS  Google Scholar 

  4. Lichter JB, Barr CL, Kennedy JL, Van Tol HH, Kidd KK, Livak KJ . A hypervariable segment in the human dopamine receptor D4 (DRD4) gene Hum Mol Genet 1993; 2: 767–773

    Article  CAS  Google Scholar 

  5. Ebstein RP, Nemanov L, Klotz I, Gritsenko I, Belmaker RH . Additional evidence for an association between the dopamine D4 receptor (D4DR) exon III repeat polymorphism and the human personality trait of Novelty Seeking Mol Psychiatry 1997; 2: 472–477

    Article  CAS  Google Scholar 

  6. Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking Nature Genet 1996; 12: 78–80

    Article  CAS  Google Scholar 

  7. Lusher JM, Chandler C, Ball D . Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: the saga continues Mol Psychiatry 2001; 6: 497–499

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Sterne JAC, Egger M . Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis J Clin Epidemiol 2001; 54: 1046–1055

    Article  CAS  Google Scholar 

  10. Hunter JE, Schmidt FL . Methods of Meta-Analysis: Correcting Error and Bias in Research Findings Sage Publications: Newbury Park, CA 1990

    Google Scholar 

  11. Field AP . Meta-analysis of correlation coefficients: a Monte Carlo comparison of fixed- and random-effects methods Psychol Meth 2001; 6: 161–180

    Article  CAS  Google Scholar 

  12. Persson ML, Wasserman D, Geijer T, Frisch A, Rockah R, Michaelovsky E et al. Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers Eur Arch Psychiatry Clin Neurosci 2000; 250: 203–206

    Article  CAS  Google Scholar 

  13. Pogue-Geile M, Ferrell R, Deka R, Debski T, Manuck S . Human novelty-seeking personality traits and dopamine D4 receptor polymorphisms: a twin and genetic association study Am J Med Genet 1998; 81: 44–48

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Jonsson EG, Nothen MM, Gustavsson JP, Neidt H, Forslund K, Mattila-Evenden M et al. Lack of association between dopamine D4 receptor gene and personality traits Psychol Med 1998; 28: 985–989

    Article  CAS  Google Scholar 

  16. Sander T, Harms H, Dufeu P, Kuhn S, Rommelspacher H, Schmidt LG . Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics Am J Med Genet 1997; 74: 483–487

    Article  CAS  Google Scholar 

  17. Bau CHD, Roman T, Almeida S, Hutz MH . Dopamine D4 receptor gene and personality dimensions in Brazilian male alcoholics Psychiatric Genet 1999; 9: 139–143

    Article  CAS  Google Scholar 

  18. Benjamin J, Osher Y, Kotler M, Gritsenko I, Nemanov L, Belmaker RH et al. TPQ personality trait of novelty seeking associated with the dopamine receptor D4 exon III (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyl transferase (COMT val → met) polymorphisms Mol Psychiatry 1999; 4: S23

    Google Scholar 

  19. Ekelund J, Lichtermann D, Jarvelin MR, Peltonen L . Association between novelty seeking and the type 4 dopamine receptor gene in a large Finnish cohort sample Am J Psychiatry 1999; 156: 1453–1455

    CAS  PubMed  Google Scholar 

  20. Gelernter J, Kranzler H, Coccaro E, Siever L, New A, Mulgrew CL . D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects Am J Hum Genet 1997; 61: 1144–1152

    Article  CAS  Google Scholar 

  21. Noble EP, Ozkaragoz TZ, Ritchie TL, Zhang XX, Belin TR, Sparkes RS . D-2 and D-4 dopamine receptor polymorphisms and personality Am J Med Genet 1998; 81: 257–267

    Article  CAS  Google Scholar 

  22. Ono Y, Manki H, Yoshimura K, Muramatsu T, Mizushima H, Higuchi S et al. Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects Am J Med Genet 1997; 74: 501–503

    Article  CAS  Google Scholar 

  23. Parsian A, Zhang ZH . Human chromosomes 11p15 and 4p12 and alcohol dependence: possible association with the GABRB1 gene Am J Med Genet 1999; 88: 533–538

    Article  CAS  Google Scholar 

  24. Tomitaka M, Tomitaka S, Otuka Y, Kim K, Matuki H, Sakamoto K et al. Association between novelty seeking and dopamine receptor D4 (DRD4) exon III polymorphism in Japanese subjects Am J Med Genet 1999; 88: 469–471

    Article  CAS  Google Scholar 

  25. Kuhn KU, Meyer K, Nothen MM, Gansicke M, Papassotiropoulos A, Maier W . Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests Am J Med Genet 1999; 88: 168–172

    Article  CAS  Google Scholar 

  26. Gebhardt C, Leisch F, Schussler P, Fuchs K, Stompe T, Sieghart W et al. Non-association of dopamine D4 and D2 receptor genes with personality in healthy individuals Psychiatr Genet 2000; 10: 131–137

    Article  CAS  Google Scholar 

  27. Herbst JH, Zonderman AB, McCrae RR, Costa PT . Do the dimensions of the temperament and character inventory map a simple genetic architecture? Evidence from molecular genetics and factor analysis Am J Psychiatry 2000; 157: 1285–1290

    Article  CAS  Google Scholar 

  28. Swift G, Larsen B, Hawi Z, Gill M . Novelty seeking traits and D4 dopamine receptors Am J Med Genet 2000; 96: 222–223

    Article  CAS  Google Scholar 

  29. Vandenbergh DJ, Zonderman AB, Wang J, Uhl GR, Costa PT . No association between novelty seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore Longitudinal Study of Aging participants Mol Psychiatry 1997; 2: 417–419

    Article  CAS  Google Scholar 

  30. Malhotra AK, Virkkunen M, Rooney W, Eggert M, Linnoila M, Goldman D . The association between the dopamine D-4 receptor (D4DR) 16 amino acid repeat polymorphism and Novelty Seeking Mol Psychiatry 1996; 1: 388–391

    CAS  PubMed  Google Scholar 

  31. Hedges L, Olkin I . Statistical Methods for Meta Analysis 1985; Academic Press: New York

    Google Scholar 

  32. Cohen J . Statistical Power Analysis for the Behavioral Sciences Erlbaum Associates: Hillsdale, NJ 1988

    Google Scholar 

  33. Ioannidis JPA, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG . Replication validity of genetic association studies Nature Genet 2001; 29: 306–309

    Article  CAS  Google Scholar 

  34. Cohen J . The earth is round (p<.05) Am Psychol 1994; 49: 997–1003

    Article  Google Scholar 

  35. Kluger AN, DeNisi A . The effects of feedback interventions on performance: a historical review, a meta-analysis, and a preliminary feedback intervention theory Psychol Bull 1996; 119: 254–284

    Article  Google Scholar 

  36. Ding Y-C, Chi H-C, Grady DL, Morishima A, Kidd JR, Kidd KK et al. Evidence of positive selection acting at the human dopamine receptor D4 gene locus PNAS 2002; 99: 309–314

    Article  CAS  Google Scholar 

  37. Okuyama Y, Ishiguro H, Nankai M, Shibuya H, Watanabe A, Arinami T . Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait Mol Psychiatry 2000; 5: 64–69

    Article  CAS  Google Scholar 

  38. Schork NJ, Fallin D, Thiel B, Xu X, Broeckel U, Jacob HJ et al. The future of genetic case-control studies Adv Genet 2001; 42: 191–212

    Article  CAS  Google Scholar 

  39. Barr CL, Wigg KG, Wu J, Zai C, Bloom S, Tannock R et al. Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder Am J Med Genet 2000; 96: 114–117

    Article  CAS  Google Scholar 

  40. Cloninger CR . A unified biosocial theory of personality and its role in the development of anxiety states: a reply to commentaries Psychiatr Dev 1988; 6: 83–120

    CAS  PubMed  Google Scholar 

  41. Benjamin J, Osher Y, Kotler M, Gritsenko I, Nemanov L, Belmaker RH et al. 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) Mol Psychiatry 2000; 5: 96–100

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Recanati Fund of the School of Business Administration at the Hebrew University (ANK) and a grant from the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities (RPE). The authors wish to thank EM Berry and two anonymous reviewers for their useful comments on an earlier draft of this paper.

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Correspondence to A N Kluger.

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Kluger, A., Siegfried, Z. & Ebstein, R. A meta-analysis of the association between DRD4 polymorphism and novelty seeking. Mol Psychiatry 7, 712–717 (2002). https://doi.org/10.1038/sj.mp.4001082

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