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
Loehlin JC . Genes and Environment in Personality Development Sage Publications: Newbury Park 1992
Cloninger CR . A systematic method for clinical description and classification of personality variants: a proposal Arch Gen Psychiatry 1987; 44: 573–588
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
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
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
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
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
Paterson AD, Sunohara GA, Kennedy JL . Dopamine D4 receptor gene: novelty or nonsense? Neuropsychopharmacology 1999; 21: 3–16
Sterne JAC, Egger M . Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis J Clin Epidemiol 2001; 54: 1046–1055
Hunter JE, Schmidt FL . Methods of Meta-Analysis: Correcting Error and Bias in Research Findings Sage Publications: Newbury Park, CA 1990
Field AP . Meta-analysis of correlation coefficients: a Monte Carlo comparison of fixed- and random-effects methods Psychol Meth 2001; 6: 161–180
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Swift G, Larsen B, Hawi Z, Gill M . Novelty seeking traits and D4 dopamine receptors Am J Med Genet 2000; 96: 222–223
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
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
Hedges L, Olkin I . Statistical Methods for Meta Analysis 1985; Academic Press: New York
Cohen J . Statistical Power Analysis for the Behavioral Sciences Erlbaum Associates: Hillsdale, NJ 1988
Ioannidis JPA, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG . Replication validity of genetic association studies Nature Genet 2001; 29: 306–309
Cohen J . The earth is round (p<.05) Am Psychol 1994; 49: 997–1003
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
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
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
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
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
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
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
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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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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DOI: https://doi.org/10.1038/sj.mp.4001082
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