Original ArticleThe 7R polymorphism in the dopamine receptor D4 gene (DRD4) is associated with financial risk taking in men☆
Introduction
Risk preferences are central to any model of human decision making, and a number of studies have documented substantial heterogeneity in individuals' willingness to take financial risks—that is, their willingness to trade off increasing variance of returns against greater expected returns (Barsky, Juster, Kimball, & Shapiro, 1997). Some individual variation in preferences can be explained by such demographic variables as sex (Barsky et al., 1997, Byrnes et al., 1999), age (Barsky et al., 1997, Donkers et al., 2001), race (Barsky et al., 1997, Fan & Xiao, 2005), religion (Barsky et al., 1997), education (Donkers et al., 2001, Grable, 2000, Grable & Joo, 2004), and socioeconomic status (Grable, 2000, Grable & Joo, 2004). However, these variables explain only a modest share of the variation. Recent work based on samples of twins showed that risk preferences are heritable (Cesarini, Johannesson, Lichtenstein, Sandewall, & Wallace, in preparation). Approximately 25% of the individual variation in risk taking, as measured by actual pension investment decisions and elicited experimentally using a gambling task, was explained by heritable differences (Cesarini, Dawes, Johannesson, Lichtenstein, & Wallace, in press). The challenge for behavioral scientists is to now identify the genetic loci associated with such risk preferences.
Risk preferences may be influenced by dopaminergic pathways in the brain. These pathways play a role in regulating the anticipation of rewards (Kelley et al., 2005, Wise, 2002) as well as the motivation for obtaining rewards (Kelley, 2004) and include the ventral tegmental area, nucleus accumbens, and the prefrontal cortex. Activation of these pathways can result in increased physiological arousal and intense feelings of well-being or pleasure (Heath, 1964, Peterson, 2005), which in turn may increase an individual's propensity to take risks. Dysfunction in these pathways can affect reward processing, motivation, and, consequently, decision making. Individuals who weigh anticipated rewards heavily may be more likely to take risks since rewards induce approach-related behaviors. Two genes known to be involved in the regulation of the dopaminergic system are the dopamine receptor D4 (DRD4) gene and the dopamine receptor D2 (DRD2) gene.
The DRD4 gene has been investigated as a candidate gene for modulating a number of approach-related behaviors (Munafo, Yalcin, Willis-Owen, & Flint, 2008), but not financial risk taking per se. Particular interest has been paid to the 48-bp variable number of tandem repeats (VNTR) polymorphism in exon III of the DRD4 gene, which consists of 2–11 repeats (Ding et al., 2002) likely involved in modulating expression (Schoots & Van Tol, 2003). Specifically, the 7-repeat (7R+) allele is associated with decreased ligand binding (Asghari et al., 1994) and has been shown to require higher levels of dopamine to produce a response of similar magnitude as compared with smaller-sized variants (Asghari et al., 1995), although its functional significance has not been definitively characterized. This blunted response to dopamine may cause inhibitory neurons that use the 7R receptor to require increased dopamine for “normal” functioning (Swanson et al., 2000) and may thus contribute to individual differences in personality and behavioral traits that are associated with dopamine levels.
Allelic variation in the DRD4 dopamine gene has been associated with novelty seeking (for a review, see Munafo et al., 2008). The presence of the 7R allele itself has been associated with alcoholism (Laucht, Becker, Blomeyer, & Schmidt, 2007), behavioral disinhibition (Congdon, Lesch, & Canli, 2008), attention deficit/hyperactivity disorder (Li, Sham, Owen, & He, 2006), pathological gambling (Perez de Castro, Ibanez, Torres, Saiz-Ruiz, & Fernandez-Piqueras, 1997), and impulsivity (Eisenberg et al., 2007). While the personality trait most widely studied in relation to DRD4 is novelty seeking, many studies have failed to find significance (Munafo et al., 2008). The most recent meta-analysis conducted also failed to support a relationship between DRD4 (VNTR) and novelty seeking as well as impulsivity (Munafo et al., 2008). However, given the small effect sizes reported for DRD4 (VNTR) on personality, small differences between studies can lead to nonsignificant findings. Indeed, there was evidence of between-study heterogeneity in this meta-analysis. The role of DRD4 (VNTR) polymorphism in personality, and specifically on approach-related behaviors, is thus inconclusive.
Another receptor for the neurotransmitter dopamine is the DRD2 gene, coded for by locus 11q23. A single-nucleotide polymorphism with two variants exists at the TaqI A locus, located downstream of DRD2 (Dubertret et al., 2004). Although its functional significance is unclear, the less frequent A1 allele has been associated with decreased D2 receptor expression in the striatum (Noble et al., 1991, Thompson et al., 1997), as compared with the A2 allele (but see Laruelle, Gelernter, & Innis, 1998). Carriers of the A1 allele, in contrast to carriers of the A2 allele, have diminished glucose metabolism in the brain (Noble, Gottschalk, Fallon, Ritchie, & Wu, 1997) and exhibit reduced dopaminergic activity (Berman & Noble, 1995). The A1 allele has been associated with substance abuse (Noble, 2003) impulsivity (Eisenberg et al., 2007), pathological gambling, novelty seeking, and sensation seeking (Ratsma, van der Stelt, Schoffelmeer, Westerveld And, & Boudewijn Gunning, 2001). A recent study examined the A1 allele in relation to personality scores measuring reward-related traits and found that women with the A1 allele were more responsive to rewards (Lee, Ham, Cho, Lee, & Shim, 2007). We predict that individuals with the A1 allele will be more risk loving as they may be more responsive to rewards.
Using a behavioral measure of risk involving real financial incentives, we examined the relationship between risk preferences and allelic variation in DRD4, focusing on the presence of the 7R allele, as well as allelic variation in DRD2 in 98 young men. An advantage of eliciting preferences experimentally, with financial incentives attached to performance, is that we can infer preferences from choices made by our subjects rather than rely on self-reported hypothetical decisions (Hertwig & Ortman, 2001).
Section snippets
Participants
Participants were recruited by flyers distributed at the Harvard University campus and via e-mail solicitation to undergraduate residential houses. A total of 98 male subjects between 18 and 23 years old participated in the study. Subjects were excluded if they reported current use of psychotropic medications or having a diagnosis of bipolar depression, pathological gambling, and/or attention deficit hyperactivity disorder. The ethnic composition of the sample was determined by self-report: 66
Results
Our subject pool was composed of 24 individuals with at least one 7R allele (7R+) and 70 individuals without the 7R allele (7R−) for DRD4. See Table 1 for summary statistics. A first test of the hypothesis comes from a mean comparison of these two groups. Regressing risk taking on a dummy variable taking a value of 1 if the individual is 7R+ and that of 0 otherwise, we found a statistically significant difference (coefficient=39.09, p=.023). On average, 7R+ individuals invest $39 more than
Discussion
We found a significant correlation between the presence of the 7R allele of the DRD4 gene and risk taking in a laboratory task. The difference in investment between individuals who are 7R+ and individuals who are 7R− is approximately half a standard deviation ($39 of $250). Our results are consistent with the hypothesis that individual variation in risk preferences may be mediated partly by allelic variants coding for differences in DRD4 receptor gene expression in key brain areas associated
Acknowledgments
We thank Peter Ellison for his help in making this study possible. We also thank Johan Almenberg, Samuel Bowles, Magnus Johannesson, Thomas Pfeiffer, David G. Rand, and Jon Wilkins for providing helpful comments and Rita Spathis for providing laboratory assistance.
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This work was supported by the Jan Wallander and Tom Hedelious Foundation (A.D.) and a National Science Foundation Graduate Research Fellowship (D.T.A.E.).
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A. Dreber and C.L. Apicella contributed equally to this work.