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 DOI: 10.1177/0956797614528338 2014 25: 1169 originally published online 18 April 2014Psychological Science

Shinobu Kitayama, Anthony King, Carolyn Yoon, Steve Tompson, Sarah Huff and Israel LiberzonInterdependent Social Orientation

) Moderates Cultural Difference in Independent VersusDRD4The Dopamine D4 Receptor Gene (  

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Research Article

Research over the past two decades has shown that when viewed from a global, cross-national perspective, cultures vary on an overarching dimension of indepen-dence versus interdependence (Greenfield, Keller, Fuligni, & Maynard, 2003; Markus & Kitayama, 1991). European Americans place a strong normative emphasis on independence of the self from others, whereas Asians put much greater emphasis on interdependence of the self with others. These normative cultural differences are reflected in more specific behavioral cultural traits; more holistic attention (Masuda & Nisbett, 2001), a greater emphasis on social (vs. personal) happiness (Kitayama, Park, Sevincer, Karasawa, & Uskul, 2009), greater sus-pension of self-interest (Kitayama & Park, 2014), and weaker motivations toward self-expression, self-esteem, and self-efficacy (Heine, Lehman, Markus, & Kitayama, 1999) are all associated with more interdependent orientations.

The culturally divergent social orientations of inde-pendence and interdependence are believed to result from acquisition of cultural norms and values. It is not certain, however, whether (and if so, how) the acquisi-tion of cultural norms may be moderated by, or inter-act with, specific genetic mechanisms. In the current work, we drew on extant research on Gene × Culture (G × C) interaction and tested whether individual dif-ferences with respect to the overarching cultural dimension of independence versus interdependence vary with polymorphisms of the dopamine D4 receptor gene (DRD4).

528338 PSSXXX10.1177/0956797614528338Kitayama et al.Dopamine D4 Receptor Gene and Cultural Differenceresearch-article2014

Corresponding Author:Shinobu Kitayama, Department of Psychology, University of Michigan, 3217 East Hall, Ann Arbor, MI 48109 E-mail: kitayama@umich.edu

The Dopamine D4 Receptor Gene (DRD4) Moderates Cultural Difference in Independent Versus Interdependent Social Orientation

Shinobu Kitayama1, Anthony King2, Carolyn Yoon3, Steve Tompson1, Sarah Huff1, and Israel Liberzon1,2

1Department of Psychology; 2Department of Psychiatry; and 3Stephen M. Ross School of Business, University of Michigan

AbstractPrior research suggests that cultural groups vary on an overarching dimension of independent versus interdependent social orientation, with European Americans being more independent, or less interdependent, than Asians. Drawing on recent evidence suggesting that the dopamine D4 receptor gene (DRD4) plays a role in modulating cultural learning, we predicted that carriers of DRD4 polymorphisms linked to increased dopamine signaling (7- or 2-repeat alleles) would show higher levels of culturally dominant social orientations, compared with noncarriers. European Americans and Asian-born Asians (total N = 398) reported their social orientation on multiple scales. They were also genotyped for DRD4. As in earlier work, European Americans were more independent, and Asian-born Asians more interdependent. This cultural difference was significantly more pronounced for carriers of the 7- or 2-repeat alleles than for noncarriers. Indeed, no cultural difference was apparent among the noncarriers. Implications for potential coevolution of genes and culture are discussed.

Keywordscross-cultural differences, genetics, social cognition, values, open materials

Received 9/29/13; Revision accepted 1/26/14

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1170 Kitayama et al.

Gene × Culture Interaction

An increasing number of studies have shown that indi-viduals can be differentially susceptible to environmental influences depending on certain genetic polymorphisms (Caspi et al., 2003; Sheese, Voelker, Rothbart, & Posner, 2007) that have been termed plasticity alleles (Belsky & Pluess, 2009). Carriers of certain plasticity markers are more vulnerable than other individuals to early traumatic events. For example, such events can increase the risk of depression and posttraumatic stress disorder later in life, but this effect is particularly apparent in individuals car-rying specific alleles in the promoter region of the sero-tonin transporter gene (5-HTTLPR; Caspi et al., 2003). Admittedly, most psychological and neurophysiological processes, including depression and posttraumatic stress disorder, are under subtle influence of a number of genes; hence, it is likely that genetic influences are both complex and polygenic. Nevertheless, the emerging work on plasticity alleles suggests that it is useful to focus ini-tially on specific key genes.

Extending this work on Gene × Environment (G × E) interaction, Kim and her colleagues have recently argued that culture constitutes a major source of environmental influences and, thus, that some cultural effects can be moderated by specific genetic variants. For example, it is normative to seek emotional or social support at times of distress in European American cultural contexts, but not in Korean cultural contexts. Kim, Sherman, Sasaki, et al. (2010) tested the hypothesis that this environmental influ-ence might be larger for carriers of a specific allele (G, as opposed to A) of the oxytocin receptor gene (OXTR) polymorphism rs53576 that had previously been linked to increased socioemotional sensitivity. Indeed, they found that European Americans who carried at least one rs53576 G allele (GG or GA genotype) were reportedly more likely to seek emotional support from other people under conditions of high distress, compared with their noncar-rier counterparts (AA genotype). However, compared with European Americans, Koreans reportedly sought less emotional support regardless of distress levels, and this tendency was not moderated by this OXTR polymor-phism. Another recent study provided further support for the G × C approach in an examination of cultural norms regarding emotion suppression (Kim et al., 2011).

Kim, Sherman, Taylor, et al. (2010) showed that a cul-tural difference in holistic attention (Masuda & Nisbett, 2001) is similarly moderated by the serotonin 1A receptor gene (HTR1A) polymorphism rs6295 (also called C(-1019)G). Compared with European Americans, Asians were found to be more holistic in attention, but this cultural difference was evident only among carriers of the G allele of HTR1A, who are more sensitive to external reinforcement than are noncarriers.

Although important, this work has so far focused on isolated behavioral traits (i.e., social support, emotion suppression, and holistic attention). Thus, an important unanswered question remains: Might specific genetic dif-ferences moderate the cultural difference in the overarch-ing dimension of independent versus interdependent social orientation?

DRD4

Yet another critical gap in the current literature on G × C interaction concerns the potential role of DRD4 in acqui-sition of cultural norms. Acquisition of normatively sanc-tioned behavioral traits, including independence and interdependence, is likely modulated by the efficiency of incentive-learning mechanisms. If that is the case, one should anticipate that cultural acquisition is moderated by genetic polymorphisms that regulate the efficiency of the central dopaminergic pathways. DRD4 polymor-phisms influence the efficiency of neural transmission in the dopamine pathways of the central nervous system, which innervate reward-processing areas of the brain, including the nucleus accumbens, the striatum, and the prefrontal cortex.

The present investigation focused on the exon 3 vari-able-number tandem repeat (VNTR) polymorphism of DRD4 (Wang et al., 2004). The number of repeats varies widely, from 2 to 11, but most common are alleles with 2, 4, and 7 repeats (i.e., 2R, 4R, and 7R alleles). Compared with the 4R allele, the 7R allele shows less in vitro dopa-mine functioning and poorer response to agonists (Asghari et al., 1995; Seeger, Schloss, & Schmidt, 2001); the 2R allele exhibits an intermediate profile. Relative to the 4R allele, the 7R and 2R alleles are associated with diminished dopamine feedback inhibition (Wang et al., 2004), which is thought to lead to higher physiological dopamine signaling capacity (Nikolova, Ferrell, Manuck, & Hariri, 2011). In fact, 7R carriers show greater ventral striatal activity (Forbes et al., 2009) and are more sensi-tive to rewards, compared with 4R carriers (Nikolova et al., 2011). Nearly all available studies on DRD4 have contrasted 7R carriers with noncarriers. These studies have largely been conducted with Western populations, in which the 2R allele is relatively uncommon. However, among Asians, the 7R allele is much less common, and instead, the 2R allele is more prevalent. Thus, Reist et al. (2007) recommended combining carriers of these two alleles in studies involving Asians. Following this recom-mendation in the study reported here, we defined our high-dopamine-signaling group to include carriers of either of these two alleles.

Furthermore, a DNA-sequencing and linkage- disequilibrium haplotype study has suggested that the 7R allele of DRD4 was likely derived from a more ancient

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Dopamine D4 Receptor Gene and Cultural Difference 1171

form (4R) 40,000 to 50,000 years ago, when humans started to expand their territory across the globe, whereas the 2R allele appeared much later, approximately 10,000 years ago (Wang et al., 2004). These alleles appear to be under active selection pressures associated with migra-tion (Chen, Burton, Greenberger, & Dmitrieva, 1999; Matthews & Butler, 2011), which suggests the intriguing possibility that DRD4 variants linked to altered dopa-mine signaling capacity could have coevolved with cul-tural forms of human adaptation. Consistent with this reasoning, related research on DNA sequencing suggests that relatively recent genetic selections, including the DRD4 VNTR, are more common than previously appre-ciated (Hawks, Wang, Cochran, Harpending, & Moyzis, 2007). Thus, evidence is converging to suggest that DRD4 must have played a significant role in the emer-gence of human cultures. We accordingly suggest that focusing on this particular gene is likely to be fruitful in the investigation of G × C interaction.

Previous work has found associations between the 7R allele of DRD4 and certain behavioral traits, including novelty seeking (Laucht, Becker, Blomeyer, & Schmidt, 2007), heavy drinking (Laucht et al., 2007), and financial risk taking (Dreber et al., 2009), but these associations have not always been replicated (Munafò, Yalcin, Willis-Owen, & Flint, 2008). Further, evidence indicates that car-riers of this variant are sometimes better socialized than noncarriers, having superior attentional control (Sheese et al., 2007) and greater prosocial orientations (Sasaki et  al., 2013). To account for the fact that the 7R allele appears to be associated with more adverse outcomes under certain conditions but with more advantageous outcomes under other conditions, some researchers have hypothesized that the 7R variant (and the 2R variant) of DRD4 functions as a plasticity allele, such that it is associ-ated with sensitivity to environmental influences (Belsky & Pluess, 2009; Sasaki et al., 2013). It is possible that which behavioral traits are associated with the 7R or 2R variant of DRD4 depends on what individuals learn from their experiences in a particular environmental or cul-tural context. Insofar as many forms of learning (includ-ing the learning of cultural norms) are mediated by reinforcement of responses, the 7 or 2R variant of DRD4 may potentiate such responses by sensitizing the carriers of the variant toward reward and reinforcement. Typically, responses that are congruous with cultural norms are likely to be reinforced. Accordingly, the 7 or 2R variant of DRD4 may be expected to be associated with greater adoption of norm-congruous responses.

The Present Work

Previous work on G × C interaction has focused on specific behavioral traits. Moreover, although several

considerations suggest that DRD4 is likely to have coevolved with culture, this work has not tested this gene. Our aim in the current work was to fill in these gaps by testing predictions on how DRD4 VNTR poly-morphisms might interact with culture to determine gen-eral social orientations. We anticipated that carriers of the 7R and 2R alleles of DRD4 would exhibit culturally domi-nant social orientations (independence for European Americans and interdependence for Asians) to a greater extent than noncarriers of these variants.

Method

Participants and procedure

We planned to recruit 200 European American (EA) and 200 Asian-born Asian (AA) students at a large Midwestern university. We stopped data collection when we roughly achieved this goal, having recruited 194 EA students (68 males and 126 females) and 204 AA students (71 males and 133 females). All of the participants responded to fli-ers posted at various campus locations. They then received an e-mail screening for eligibility. To qualify as an EA participant, a person had to be of European ances-try and to have been born and raised in the United States; to qualify as an AA participant, a person had to have been born in an East Asian country (i.e., China, Japan, Korea, and Taiwan) and to have spent no more than 10 years in the United States. Eligible students were invited to participate in a study on the relationships among per-sonality, genes, and well-being. Either individually or in small groups of 2 to 10 individuals, they were asked to complete a series of computerized questionnaires and then provided a saliva sample. They received $25 for their participation. The mean age of the participants was 20.3 years (SD = 1.2). A majority of the AA participants (82%) had spent no more than 7 years in the United States (M = 4.6 years, SD = 3.5).

Genotyping

An Oragene saliva kit (OG-500) was used for saliva collection (DNA Genotek, Kanata, Ontario, Canada). Genomic DNA was extracted using a high-capacity membrane-based column (QuickGene810, AutoGen, Inc., Holliston, MA) and was quantitated using an A260/A280 ratio with a NanoDrop spectrophotometer (ThermoScientific, Inc., Wilmington, DE) and agarose gel electrophoresis. The DRD4 VNTR polymorphism was amplified, with 0.2 µM of DRD4 forward primer 5′-GCGACTACGTGGTCTACTCG and 0.2 µM of DRD4 reverse primer 5′-AGGACCCTCATGGCCTTG (Lichter et al., 1993), using the Roche GC-Rich PCR System ampli-fication buffer (Roche Applied Science, Inc., Mannheim,

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1172 Kitayama et al.

Germany) and 20 ng of genomic DNA in a volume of 25 µl. The samples were heated in a Stratagene thermo-cycler (Life Technologies, Inc., Grand Island, NY) at 95 °C for 3 min, then cycled 40 times at 95 °C for 20 s, 57 °C for 20 s, and 72 °C for 1 min, followed by 72 °C for 3 min. Polymerase chain reaction products were sepa-rated and visualized on a 2% agarose gel (type 1-A, Sigma, St. Louis, MO) stained with ethidium bromide.

Out of the total sample, 377 participants were success-fully genotyped for DRD4. Frequencies of the common DRD4 VNTR alleles were in line with previous findings (Chen et al., 1999): for EA participants, 6.9% 2R, 6.9% 3R, 63.5% 4R, 1.3% 5R, 17.2% 7R, 2.4% 8R, and 1.9% 10R; for AA participants, 17.3% 2R, 1.6% 3R, 76.6% 4R, 1.9% 5R, 0.3% 6R, and 2.4% 7R. As in previous work (Reist et al., 2007; Sasaki et al., 2013), carriers of the 7R and 2R alleles (associated with relatively high dopamine signaling; 84 EA and 63 AA participants) were compared with a lower-dopamine- signaling group of noncarriers of these alleles (mainly the 4R/4R genotype, as well as more rare variants including the 3R, 5R, 6R, 8R, and 10R alleles; 105 EA and 125 AA participants).

Scales

We administered a series of questionnaires, including the six scales that are pertinent to the present investigation. As we show later in this section, all scales had acceptable reliabilities in both cultural groups and comparable reli-abilities across groups.

To assess independent social orientation, we used the following four scales.

•• Independent Subscale of Singelis’s (1994) Self-Construal Scale: This subscale is composed of 15 items designed to assess the respondent’s construal of the self as independent. Sample items include, “I enjoy being unique and different from others in many respects” and “I feel it is important for me to act as an independent person” (αs = .71 and .72 for EA and AA participants, respectively).

•• General Self-Efficacy Scale (Schwarzer, Mueller, & Greenglass, 1999): This scale consists of 10 items measuring beliefs about one’s personal agency and action control. Sample items include, “I can usually handle whatever comes my way” and “I am confi-dent that I could deal efficiently with unexpected events” (αs = .85 and .81 for EA and AA partici-pants, respectively).

•• Self-Esteem Scale (Rosenberg, 1965): This is a 10-item scale, which measures an individual’s per-ception of his or her own self-esteem. Sample items include, “On the whole, I am satisfied with myself” and “I am able to do things as well as most

other people” (αs = .86 and .90 for EA and AA participants, respectively).

•• Value of Expression Questionnaire (Kim & Sherman, 2007): This scale is composed of 11 items designed to assess the extent to which the respondent values self-expression in both behavior and beliefs. Sample items include, “Being able to make my own choice is important to me” and “The freedom of speech is the most important right” (αs  = .77 and .72 for EA and AA participants, respectively).

To assess interdependent social orientation, we used the following two scales.

•• Interdependent Subscale of Singelis’s (1994) Self-Construal Scale: This subscale measures the respondent’s construal of the self as interdepen-dent. Sample items include, “I will sacrifice my self interest for the benefit of the group I am in” and “My happiness depends on the happiness of those around me” (αs = .68 and .72 for EA and AA par-ticipants, respectively).

•• Analysis-Holism Scale (Choi, Koo, & Choi, 2007): This scale is composed of 24 items designed to assess the extent to which an individual has a holistic cognitive style. Sample items include, “It is more desirable to take the middle ground than go to extremes” and “It is not possible to understand the parts without considering the whole picture” (αs = .69 and .72 for EA and AA participants, respectively).

Indices of social orientation

We performed factor analyses to construct indices of social orientation based on six variables derived from the scales just described: independent self-construal, interde-pendent self-construal, value of self-expression, holistic cognitive style, self-esteem, and self-efficacy. The first four variables were available for all 398 participants, but the last two variables were available for only 275 partici-pants, as 123 participants did not fill out the scales for self-esteem and self-efficacy. We thus performed two fac-tor analyses: One included just the 275 participants for whom all six variables were available, and the other included all 398 participants, with the missing two vari-ables imputed using multiple regression. The imputation for the two variables was based on ethnicity, scores on the remaining four scales included in the current report, and scores on four scales included in the study for other purposes (see Supplementary Methods in the Supple-mental Material available online), which accounted for 38% of the variance for both self-esteem and self-efficacy.

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Dopamine D4 Receptor Gene and Cultural Difference 1173

We found no substantive differences between the factor analyses including and excluding the 123 additional respondents; we therefore used factor scores based on the analyses including them (Table S1 in the Supplemental Material summarizes the results of the factor analysis without imputation).

As indicated by the results in Table 1, the indepen-dence factor score was defined by independent self- construal, self-esteem, self-efficacy, and value of self-expression, whereas the interdependence factor score was defined by interdependent self-construal and holistic cognitive style.

Results

First, we analyzed the independence-factor scores in an analysis of variance with two between-subjects variables, culture (EA vs. AA) and DRD4 (7/2R-allele carriers vs. 7/2R-allele noncarriers). This analysis revealed a signifi-cant main effect of culture, F(1, 373) = 9.81, p < .002; EA participants were more independent than AA partici-pants. In addition, the predicted Culture × DRD4 interac-tion was significant, F(1, 373) = 5.77, p < .02. There was a strong cultural difference in independence in the pre-dicted direction among the 7/2R carriers, with EA partici-pants significantly more independent than AA participants, F(1, 373) = 12.49, p < .001; in contrast, this cultural differ-ence was negligible for the 7/2R noncarriers, F < 1. The same pattern was evident for each of the four variables that made up the independence factor (Table 2).

An analysis of variance that examined the interdependence- factor scores also revealed a significant main effect of culture, F(1, 373) = 7.54, p < .01; AA participants were more interdependent than EA partici-pants. This main effect was marginally qualified by the predicted Culture × DRD4 interaction, F(1, 373) = 3.15, p < .08. Whereas the cultural difference was significant among the 7/2R carriers, F(1, 373) = 8.33, p < .005, no such difference was evident for the 7/2R noncarriers, F < 1 (see Table 2).

For parsimony, we created a single composite index of social orientation, by subtracting the interdependence-factor score from the independence-factor score. Figure 1 summarizes the resulting values. As predicted, we found a significant difference between the EA and AA partici-pants on the social-orientation index, F(1, 373) = 18.14, p < .001, with EA participants being more independent and AA participants being more interdependent. More important, there was a significant interaction between culture and DRD4, F(1, 373) = 9.15, p < .003, ηp

2 = .024, indicating that the allelic variations of DRD4 differentially affected social orientation in the two cultural groups. Specifically, the cultural difference was sizable for the 7/2R carriers, F(1, 373) = 21.53, p < .001, but it was negligible for the 7/2R noncarriers, F < 1. Among EA par-ticipants, the 7/2R carriers were significantly more inde-pendent than the noncarriers, F(1, 373) = 4.30, p < .04, and, conversely, among AA participants, the 7/2R carriers were significantly more interdependent than the 7/2R noncarriers, F(1, 373) = 4.86, p < .03.

All analyses were repeated comparing 7/2R carriers with the homogeneous group of 4/4 homozygotes only, and similar results were obtained (see Supplementary Results in the Supplemental Material). These results indi-cate that the critical effects were not driven by more rare alleles. Moreover, no significant effects involving gender were observed. Additional analyses showed that the two alleles linked to increased dopamine signaling (7R and 2R) were very similar in their effects on independent and interdependent social orientation (see Supplementary Results).

Discussion

Gene × Culture interaction

Our data provide robust evidence that the well-replicated cultural difference on the overarching dimension of inde-pendence and interdependence is moderated by the 7R and 2R alleles of DRD4. This study extends the current

Table 1. Factor Loadings From a Factor Analysis of the Variables Used to Assess Independent and Interdependent Social Orientation

Variable

All participants European Americans Asian-born Asians

Factor 1 Factor 2 Factor 1 Factor 2 Factor 1 Factor 2

Independent self-construal .803 –.054 .830 –.003 .799 –.140Self-esteem .743 .034 .741 .107 .733 .016Self-efficacy .812 .078 .843 .136 .774 .082Value of self-expression .659 –.117 .652 –.157 .664 –.087Interdependent self-construal –.110 .800 –.097 .807 –.098 .793Holistic cognitive style .074 .815 .132 .770 .032 .833

Note: Factors were extracted with principal component analysis and subsequently rotated with varimax rotation with Kaiser normalization.

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1174 Kitayama et al.

literature on G × C interaction (Kim et al., 2011; Kim, Sherman, Sasaki, et al., 2010; Kim, Sherman, Taylor, et al., 2010), a special case of G × E interaction, by showing

that the general social-orientation dimension is subject to such an effect. Further, ours is the first study to demon-strate the role of DRD4 in modulating cultural influences. Moreover, our results are consistent with existing evi-dence that norm-congruous behaviors are associated with the 7R and 2R allelic variants of DRD4 (Sasaki et al., 2013; Zhong et al., 2010).

The current data are in line with our more general expectation that DRD4 is particularly important in the investigation of G × C interaction because its variants are likely to have coevolved with modern human cultures. Because of our exclusive focus on this candidate gene, our sample size (total N = 398) was adequate even though it would not be for genomewide-association studies that simultaneously test numerous alleles. It is indeed reassur-ing that the pattern of our findings was highly consistent across the six subdimensions of independence and inter-dependence (results summarized in Table 2).

Two interesting aspects of our findings must be noted. First, we observed no significant cultural difference in social orientation in the noncarrier groups. Although it is difficult to make strong inferences from null findings, one might argue that there are other genes that suppress (as well as enhance) plasticity with respect to cultural reward contingencies. Moreover, there might be addi-tional mechanisms of cultural learning, such as mimicry or imitation (Newson, Richerson, & Boyd, 2007), obser-vational learning (Tomasello, 1999), and anxiety reduc-tion (Greenberg, Solomon, & Pyszczynski, 1997), to name just a few. These different mechanisms are likely to be influenced by different genes. It is possible that whereas the cultural difference in social orientation is moderated

Table 2. Mean Scores for the Variables Assessing Social Orientation and Analysis of Variance Results

Construct and variable

Mean score

Culture × DRD4Noncarriers Carriers

EA AA EA AA F p ηp2

Independent social orientation Independent self-construal 4.80 (0.634) 4.94 (0.608) 4.91 (0.643) 4.74 (0.656) F(1, 373) = 5.49 < .020 .015 Self-esteem 2.98 (0.511) 3.00 (0.440) 3.10 (0.529) 2.87 (0.539) F(1, 253) = 3.34 < .069 .013 Self-efficacy 3.18 (0.369) 3.11 (0.340) 3.29 (0.402) 3.03 (0.321) F(1, 253) = 4.05 < .045 .016 Value of self-expression 5.50 (0.866) 5.47 (0.790) 5.73 (0.869) 5.38 (0.846) F(1, 373) = 3.27 < .071 .009 Independence factor 0.033 (.935) –0.044 (0.967) 0.247 (1.047) –0.336 (1.039) F(1, 373) = 5.77 < .02 .015Interdependent social orientation Interdependent self-construal 4.95 (0.563) 5.07 (0.593) 4.82 (0.596) 5.07 (0.539) F(1, 373) = 1.09 n.s. .003 Holistic cognitive style 4.88 (0.460) 4.89 (0.484) 4.84 (0.483) 5.03 (0.443) F(1, 373) = 3.45 < .064 .009 Interdependence factor –0.035 (0.967) 0.068 (1.032) –0.237 (1.010) 0.242 (0.959) F(1, 373) = 3.15 < .08 .008

Note: Standard deviations are given in parentheses. Reliabilities and mean scores were calculated separately for European American (EA) and Asian-born Asian (AA) participants. Within these cultural groups, mean scores were calculated separately for carriers and noncarriers of the 2-repeat or 7-repeat allele of the exon 3 variable-number tandem repeat polymorphism of the dopamine D4 receptor gene (DRD4). Analysis of variance results are presented for the interaction of cultural group and carrier status. The scales of self-esteem and self-efficacy were not included among the questionnaires completed by 123 participants (104 EA and 19 AA). All 398 subjects filled out the remaining scales.

–0.8

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European Americans Asian-Born Asians

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Noncarrier Carrier

Fig. 1. Mean value of the composite measure of social orientation (independent-factor score – interdependent-factor score) as a function of culture and exon 3 variable-number tandem repeat (VNTR) polymor-phism of the dopamine D4 receptor gene (DRD4; carrier vs. noncarrier of the 2 or 7 repeat). Error bars represent ±1 SE.

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Dopamine D4 Receptor Gene and Cultural Difference 1175

by DRD4 when social orientation is measured with explicit belief-based measures (as in the current work), it may be moderated by other genes when it is assessed with other behavioral or neural indicators. This implies that noncarriers of the 7R or 2R allele of DRD4 might still show culturally normative psychological tendencies when assessed with different indicators of social orienta-tion. Further work is needed to shed light on the specific mechanisms of cultural acquisition. Clearly, any cultural group is not homogeneous, and this variability by itself calls for systematic investigation in future research.

Second, it did not appear that length of time spent by Asians in the United States as adults strongly affected their social orientation (see Supplementary Results in the Supplemental Material). As noted earlier, a vast majority of our AA participants had spent no more than 7 years in the United States, and none spent more than 10 years. It is likely that nearly all of our AA participants came to the United States only after puberty. Because immigrants are flexibly influenced by their host culture only if they immigrate in early childhood (Cheung, Chudek, & Heine, 2011; Minoura, 1992), our AA participants may not have been acculturated into the mainstream American culture regardless of the length of their stay in the United States. Well-acculturated Asian Americans may show a pattern that is more similar to the one we observed for European Americans (Kim, Sherman, Sasaki, et al., 2010).

DRD4: a double-edged sword?

In seeming contrast to this new evidence for the asso-ciation between the 7R and 2R alleles of DRD4 and cul-turally sanctioned social orientations, previous work suggests that these alleles are sometimes linked to less socially sanctioned behaviors, such as financial risk tak-ing and heavy drinking (Dreber et al., 2009). These latter behaviors are arguably norm incongruous and unlikely to be culturally sanctioned. How can it be that the 7R and 2R alleles of DRD4 are associated with both norm- congruous behaviors (culturally sanctioned social orien-tations) and norm-incongruous behaviors (e.g., risk seeking and heavy drinking)?

It is possible that both types of associations exist, but that they emerge under different social circumstances. Among children, the 7R allele of DRD4 is associated with externalizing behaviors under poor parenting condi-tions, but it is associated with better adjustment under conditions of better parenting (Sheese et al., 2007; van IJzendoorn et al., 2011). It might be the case that the 7R and 2R alleles are associated with greater acquisition of culturally sanctioned social orientations under generally favorable conditions of socialization, such as careful guid-ance and scaffolding of norm-congruous behaviors by socialization agents (e.g., parents, relatives, neighbors),

but with markedly different, deviant behaviors (e.g., delin-quency and risk proneness) under unfavorable social conditions or adversity, which might “reward” externaliza-tion or risk taking. Under favorable conditions, individuals with the 7R or 2R allele of DRD4 may be expected to acquire behaviors that are considered socially desirable (i.e., independent behaviors in European American cul-ture and interdependent behaviors in Asian culture). This might explain why the linkage between the 7R and 2R alleles of DRD4 and culturally sanctioned social orienta-tions was observed among our participants, who presum-ably had relatively privileged social upbringings, given that they were all students at an elite U.S. university.

Coevolution of genes and culture

The current work has some bearing on the coevolution of cultural systems and genetic polymorphisms. Chiao and Blizinsky (2010) suggested that certain alleles of the 5-HTTLPR polymorphism of the serotonin transporter gene might have coevolved with cultural collectivism and individualism. They argued that although a short allele of 5-HTTLPR is linked to anxiety and depression, especially under traumatic life conditions (Caspi et al., 2003), this genetic risk might be mitigated by cultural collectivism, which involves more caring social relations and support networks. Cultural collectivism might therefore “buffer genetically susceptible populations from increased prev-alence of affective disorders” (p. 529), which in turn might lead to a relatively high prevalence of the short allele of 5-HTTLPR.

Likewise, it is possible that DRD4 coevolved with culture. The prevalence of the 7R allele increases as a func-tion of the distance that cultural groups emigrated in the evolutionary past (Chen et al., 1999). It might be the case that the genetically increased reward sensitivity of 7R carri-ers motivates emigration or, alternatively, increases their likelihood of survival and reproduction in harsh, primitive conditions of the frontier (Kitayama, Conway, Pietromonaco, & Park, 2010). It is also possible, in view of the current evi-dence, that the increased reward sensitivity of 7R carriers was instrumental in forging norm-based cooperation within culture, which in turn could increase the likelihood of sur-vival for the cultural group as a whole (Nowak, Tarnita, & Wilson, 2010), especially under harsh frontier conditions.

Future directions

One important agenda for future work is to test whether the current results can be replicated using behavioral and neu-ral indicators of social orientation that are unlikely to be influenced by self-presentation (Kitayama & Uskul, 2011). Further, it will be important to test both individual and potentially cumulative effects of a wider range of genes

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1176 Kitayama et al.

pertaining not only to the dopamine system (Nikolova et al., 2011), but also to the serotonin (Caspi et  al., 2003; Kim, Sherman, Taylor, et al., 2010) and oxytocin (Kim, Sherman, Sasaki, et al., 2010) systems, as mechanisms without a direct connection to dopamine could also contribute to social ori-entation (Belsky & Pluess, 2009). This work will also benefit from thorough analysis of the population-level prevalence of polymorphisms of these genes, which typically varies widely across regions and ethnic groups (Chiao & Blizinsky, 2010). Last but not least, it will also be worth testing whether the cultural variations in the values and beliefs pertaining to independence and interdependence are most likely to arise when carriers of gene variants with high dopamine signal-ing capacity are socialized under favorable conditions that are characterized by attentive parenting and an integrated community.

Author Contributions

S. Kitayama, A. King, C. Yoon, I. Liberzon, and S. Tompson were actively involved in conceiving and designing the study. S. Tompson and S. Huff collected, analyzed, and interpreted the data under the supervision of S. Kitayama, A. King, C. Yoon, and I. Liberzon. S. Kitayama drafted the manuscript, and all remaining authors provided critical revisions. All the authors approved the final version of the manuscript for submission.

Declaration of Conflicting Interests

The authors declared that they had no conflicts of interest with respect to their authorship or the publication of this article.

Supplemental Material

Additional supporting information may be found at http://pss .sagepub.com/content/by/supplemental-data

Open Practices

Our institutional review board has determined that the study team may upload data only from subjects who have given per-mission to have their data used “without restriction,” which is indicated by initialing this provision on the consent form. In the present case, we did not obtain such permission, so we cannot upload our data to any public repository. The materials used have been made publicly available and can be accessed at http://hdl.handle.net/2027.42/106030. The complete Open Practices Disclosure for this article can be found at http://pss .sagepub.com/content/by/supplemental-data. This article has received the badge for Open Materials. More information about the Open Practices badges can be found at https://osf.io/tvyxz/wiki/view/ and http://pss.sagepub.com/content/25/1/3.full.

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