Article

A meta-analysis of the association between DRD4 polymorphism and Novelty Seeking

School of Business Administration, The Hebrew University of Jerusalem, Mt Scopus, Jerusalem, Israel.
Molecular Psychiatry (Impact Factor: 14.5). 02/2002; 7(7):712-7. DOI: 10.1038/sj.mp.4001082
Source: PubMed
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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Available from: Avraham N Kluger
Molecular Psychiatry (2002) 7, 712–717
2002 Nature Publishing Group All rights reserved 1359-4184/02 $25.00
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ORIGINAL RESEARCH ARTICLE
A meta-analysis of the association between DRD4
polymorphism and novelty seeking
AN Kluger
1
, Z Siegfried
2
and RP Ebstein
3
1
School of Business Administration, The Hebrew University of Jerusalem, Jerusalem, Israel;
2
Department of Human
Nutrition and Metabolism, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel;
3
Research
Laboratory, S Herzog Memorial Hospital, Jerusalem, Israel
A meta-analytical review of 20 studies (n = 3907) of the association between DRD4 polymor-
phism 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 moder-
ators, theory-driven research for potential interaction, coupled with larger sample sizes should
be employed. The growing availability of powerful statistical techniques, high-throughput gen-
otyping and large numbers of polymorphic markers such as single nucleotide polymorphisms
makes such proposed studies increasingly feasible.
Molecular Psychiatry (2002) 7, 712–717. doi:10.1038/sj.mp.4001082
Keywords: meta-analysis; personality; polymorphism (genetics); dopamine D4 receptor; novelty
seeking; questionnaire
Evidence based on twin and adoption studies suggests
that human personality traits are partially heritable.
1
However, the specific genes responsible for trait varia-
bility are not known. Human personality is usually
assessed using self-report questionnaires and one such
questionnaire is the tridimensional personality ques-
tionnaire or TPQ designed by Cloninger
2
which has
been widely used in genetic studies. The TPQ is based
on a biosocial theory of personality that draws on
human and animal work to suggest that behavior is
mediated by certain neurotransmitters which underlie
three basic and largely heritable dimensions, called
‘Novelty Seeking (NS),’ ‘Harm Avoidance (HA)’ and
‘Reward Dependence (RD).’ Cloninger suggested that
the trait of NS is mediated by genetic variability in
dopamine transmission whereas HA is mediated by
serotonergic transmission and RD by noradrenergic
transmission. Research undertaken to test this hypoth-
esis identified the dopamine D4 receptor gene (DRD4)
exon III polymorphism
3,4
as a candidate gene that may
be associated with the NS trait.
5,6
This polymorphism
is an unusually variable repeat region in the third cyto-
plasmic loop of the receptor coding for 16 amino acids.
Correspondence: AN Kluger, School of Business Administration,
The Hebrew University, Mt Scopus, Jerusalem 91905, Israel.
E-mail: Avraham.Klugerhuji.ac.il
Received 12 November 2001; revised 11 January 2002; accepted
16 January 2002
The two most common repeats in most populations are
the 4 and 7. However, reports concerning the associ-
ation between the DRD4 exon III polymorphism and
the personality trait of NS have yielded an inconsistent
pattern. Whereas initial reports suggested that long
alleles (mostly representing the 7 repeat since the 6 and
8 repeats are relatively rare) are associated with higher
scores on the personality scale of NS, others have sug-
gested that either the two are not associated or even
the short alleles (usually 4 repeats) are associated with
higher NS scores. This inconsistent pattern has been
noted in several review articles which offered a narra-
tive review of the pertinent reports.
7,8
Yet, these narra-
tive reviews were inconclusive as well.
An alternative to the narrative review is a meta-
analysis that integrates all the available data numeri-
cally. A meta-analysis has three advantages over the
narrative review. First, it can assess the effect (the
strength of the association) in the population more
efficiently than any of the original reports by utilizing
the increase in sample size. Second, it can assess the
variability of the effect in the population to determine
whether inconsistent reports reflect mere statistical
fluctuation (ie, no two reports are likely to yield ident-
ical results even if in the population the effect is con-
stant, merely due to random sampling errors). Third, if
it is determined that some of the between-studies
inconsistency is not random, then one can investigate
the potential moderators (or modulating factors) of the
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association under investigation. However, meta-ana-
lytic techniques have their own methodological limi-
tationsincluding a potential publication bias against
negative or non-signicant results,
9
mixing different
types of variables as if they were measuring the same
construct,
10
and statistical biases in the meta-analysis
estimates.
11
Thus, our goal in this paper is to review
the literature regarding the link between the DRD4
exon III polymorphism and NS utilizing the advantages
of the meta-analysis, while safeguarding as much as
possible against the potential limitations of the meta-
analysis techniques.
To reap the maximum benet from a meta-analysis,
as many reports with similar methodology as possible
should be reviewed. In the pertinent literature regard-
ing the DRD4 polymorphism and NS, several types of
research designs were used both with regards to the
grouping of the genetic polymorphism and with
regards to the specic instrument used for personality
assessment. Comparison between genetic polymor-
phisms is sometimes assessed by comparing most com-
mon specic genotypes (eg, 4,4 vs 4,7) and at times by
using a short vs long classication (25 vs 68
repeats). Since most studies used the short vs long
scheme we used this classication scheme as well.
Most of the literature has used Cloningers TPQ instru-
ment and only a few used the NEO-PI
1214
and the Kar-
olinska Scale of Personality.
15
Therefore, to ensure
homogeneity (to avoid the problem of mixing apple
and oranges
10
) we restricted our analysis only to those
investigations employing the TPQ. The TPQ also meas-
ures other traits: HA and RD. If the DRD4 polymor-
phism has a unique association with NS, one would
expect no association with the other traits. Hence,
wherever reported we also analyzed the association
between the presence of long vs short alleles with HA
and RD.
Methods
We conducted a computerized search (Medline) with
the following search criteria: (Personality or Novelty
Seeking or Extroversion) and (DRD4 or Poly-
morphism). In addition, we used back references from
identied papers to nd as many pertinent papers as
possible. We found a total of 19 relevant pap-
ers
5,6,13,14,1630
(Table 1) yielding 20 different studies.
For each report we calculated the strength of the
association. Given that the association is calculated
between a dichotomous variable (long vs short allele)
and a continuous variable (NS), the appropriate index
of effect size is the statistics d that measures the stan-
dardized difference in mean NS scores between people
who have and people who do not have the long allele.
That is, in a given study a d of 1 means that the mean
NS of those who have the long allele was one standard
deviation higher on NS than the mean of those who do
not have the long allele. A d of zero means that in a
given study there was absolutely no mean difference
in NS scores between those who carry the long allele
and those who do not. Finally, a d of 0.5, for example,
Molecular Psychiatry
Table 1 Studies included in a meta-analysis of association
between the presence of the DRD4 exon III long allele and
novelty seeking
Study n d Alleles
compared
Benjamin et al (1996)
b
315 0.40 68 p/a
Ebstein et al (1996) 124 0.58 7 p/a
Malhotra et al (1996) 138 0.42 7 p/a
Alcoholics
Malhotra et al (1996) 193 0.12 7 p/a
Non Alcoholics
Ebstein et al (1997) 94 0.24 7 p/a
Gelernter et al (1997) 321 0.30 7 p/a
Ono et al (1997) 153 0.30 56 p/a
Sanders et al (1997) 92 0.11 7 p/a
Vadenbergh et al 188 0.01 25 vs 68
(1997)
a
Noble et al (1998) 119 0.37 7 p/a
Pogue-Geile et al (1998) 281 0.04 7 p/a
Bau et al (1999) 110 0.28 7 p/a
Ekelund et al (1999) 190 0.39 7 p/a
Kuhn et al (1999) 190 0.05 7 p/a
Strobel et al (1999) 136 0.63 7 p/a
Tomitaka et al (1999)
d
69 0.86 57 p/a
Benjamin et al (2000)
c
454 0.07 7 p/a
Gebhardt et al (2000) 106 0.26 7 p/a
Herbst et al (2000) 587 0.02 7 p/a
Swift et al (2000) 47 0.22 68 p/a
p/a = present/absent.
a
NS is estimated from a larger sample.
b
Corrected personality for age, sex, & ethnicity.
c
Corrected personality for age & sex.
d
There is a discrepancy in the d calculated on the basis of
the summary data (means or standard deviations) and the t
value in the paper; the d in this table is based on means and
standard deviation but the d calculated on the basis t-score
suggests d = 0.62.
would mean that the mean NS of the carrier of the long
allele was lower by half a standard deviation than the
mean NS score of those who do not carry a long allele.
Note that d can be converted to a correlation coefcient
(Pearsons r) but the choice of meta-analysts is to work
with the unit of measurement that is characteristic of
the literature.
There are two slightly different meta-analytical
approaches to combine research data. Whereas typi-
cally the conclusions produced by the various methods
are similar, in cases where the effect sizes are small
(the association exists but is weak), the methods can
diverge in their conclusions.
11
Of course, ones trust in
the meta-analytic results will be enhanced if it is
shown that the conclusion is independent of the
methods. Thus, we have applied two methods that can
potentially differ in their conclusions. Specically, we
used both the methods of Hedges and Olkin
31
and those
of Hunter and Schmidt.
10
The differences in estimates
are explained in the Results section.
For each study we computed d (Hunter & Schmidts
method) and d+ (Hedges & Olkins method) from the
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reported means and standard deviations. Whenever a
report did not provide means and standard deviations,
but provided a t-test score, we computed d directly
from t. Whenever a report provided means for sub-
groups of either people or sub-scales, we rst averaged
the means and variances of NS across the sub groups,
or sub scales, to derive mean and standard deviation
NS for those with and those without the long allele.
We performed this aggregation with one exception
because it provided two large samples; one for
alcoholics and one for non-alcoholics (see coding
below). When a study dichotomized NS to high/low
score, we treated the proportion differences as mean
differences by calculating standard deviation for pro-
portions.
Finally, we coded for each study the following
demographic variables that according to the literature
could potentially moderate the association: mean age
of the sample, proportion of males in the sample,
whether the sample was based on alcoholics (1) or non-
alcoholic population (0), and whether the sample was
from continental Europe (1) or not (0). The later vari-
able was chosen because most of the negative reports
came from continental Europe.
Results
Prior to performing the meta-analysis we explored the
distribution of the literature with a stem-and-leaf dis-
play (Table 2). The results in the literature appear to
be normally distributed without noticeable outliers
that can bias the meta-analysis estimates. This table
helps to obtain a birds eye view that suggests that the
entire literature is distributed between moderate-nega-
tive effects to moderate-positive effects (d 0.2 is
considered weak, 0.2 d 0.5 is moderate and d
0.8 is strong
32
).
The distribution of the results in this literature
(Table 2) suggests that this literature does not suffer
from a serious publication bias because many reports
were published despite reporting either negative
effects or non-signicant effects. This observation was
further explored with a funnel plot
9
with d values on
Table 2 Stem-and-leaf display of raw d values of the associ-
ation between presence of long DRD4 allele and NS
0.8 6
0.6 3
0.4 0 8
0.2 24807
0.0 1451
0.0 2 7 2
0.2 9 0 6
0.4 2
This display shows all the raw data (d values). For example,
the d value of Strobel et al (1999) is 0.63 and is represented
as 3 under the stem of 0.6, and the d value of Ebstein et al
(1996) is 0.58 and it is represented as 8 under the stem of 0.4
(that includes values between 0.40 and 0.59).
one axis and standard errors on the other axis. As can
be expected from the almost normal distribution
shown in Table 2, the funnel plot was largely sym-
metrical ruling out a serious publication bias. This
increases the condence one can place in the meta-ana-
lytical results presented next.
Both meta-analytical methods suggested similar con-
clusions (Table 3). The mean difference in NS between
those who carry the DRD4 long allele and those who
do not carry it is negligible (about 1/20 of a standard
deviation). The condence interval for the mean
includes zero (eg, the mean effect in the literature is not
statistically signicantly different from zero). However,
both methods indicate that whereas the mean effect is
close to zero, the differences between studies are due
in part to true heterogeneity, ie, different studies esti-
mating different true underlying association para-
meters. Specically, some studies nd positive associ-
ation and some studies nd negative association and
this divergence in results is not likely to be random
(the Q-statistic is highly signicant for the Hedges &
Olkin method and according to the Hunter & Schmidts
method only 24.8% of the variability in results across
studies could be attributed to random sampling error).
Hence both methods strongly indicate that there are
unknown moderators of the association between DRD4
polymorphism and NS.
Given the statistical evidence for the presence of
moderators, we calculated the weighted correlation
between the coded variables and d (Table 4). The
weights for the correlations are based on the sample
size of each effect.
31
using the WEIGHT option of the
readily available PROC CORR procedure in SAS.
All the demographic variables showed non-signi-
cant trends (weighted rs) of attenuating the results
(Table 4). The strongest trend is for samples from Con-
tinental Europe, which are most likely to yield negative
association between the long allele and NS. Similarly,
the older the mean age of the sample the weaker, or
even negative, were the associations between the long
allele and NS. The other potential moderators yielded
non-signicant and extremely small correlations.
Discussion
Our results are consistent with a recent trend found in
36 meta-analyses that led to the conclusion that The
rst study often suggests a stronger genetic effect than
is found by subsequent studies (p 1).
33
Indeed, the
mean association between the DRD4 long allele, on the
basis of data aggregated over almost 4000 individuals,
is negligible and statistically not signicant. This con-
clusion is strengthened by noting that the association
between DRD4 polymorphism and NS is similar in
magnitude (Table 3) to the association between DRD4
polymorphism and other traits (HA, RD; 0.14, 0.10,
respectively). These were not the primary targets of
investigation and yet yielded similar and numerically
stronger effects. These could be considered as control
variables that should show weaker effects than the one
found for NS. Thus the pattern of results suggests, con-
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Table 3 Meta-analytic estimates of the mean association between the presence of the DRD4 exon III long allele and person-
ality measures
Hedges & Olkins method Hunter & Schmidts method
Trait n k d LCL UCL Q P d LCL UCL % EV
NS 3907 20 0.05 0.02 0.11 64.0 8.7*10
7
0.06 0.05 0.16 24.8
HA 1127 9 0.14 0.27 0.01 11.8 0.16 0.14 0.22 0.05 58.7
RD 1127 9 0.11 0.01 0.24 6.5 0.58 0.10 ––100
n, Number of people across all studies; k, number of samples; LCL, 95% lower condence limit; UCL, 95% upper condence
limit; % EV, percent of variance among samples that can be attributed to random sampling error. When % EV is estimated to
be 100% it is assumed that all variance between studies is random and thus no variability in true d is expected, hence LCL
and UCL, for true d, are identical to d. Tomitaka et al (1999) mentioned data for HA and RD in their paper but did not report
it there. Dr Tomitaka generously provided us with these data. Q, Q-statistics of homogeneity; P, probability of observing Q
under the null hypothesis of homogeneity.
Table 4 Moderator analysis of the link between sample
characteristics and strength of the association between DRD4
polymorphism and NS
Moderator k r P
Mean age of sample 20 0.23 0.36
Sample from Continental Europe 20 0.27 0.25
% Male in sample 19 0.06 0.79
Sample of alcoholics 20 0.11 0.64
k, Number of samples; r, sample weighted correlation coef-
cient.
trary to initial reports, and consistent with recent
reviews
8
that there is no simple association between
DRD4 polymorphism and NS.
However, the variability in the direction and magni-
tude of the associations between DRD4 polymorphism
and NS found in the literature indicates that there are
as yet unknown causes for nding weak to moderate
positive effects in some studies, null ndings in some
other studies, and weak negative effects in yet other
studies. Some of this variability was estimated to be
due to true heterogeneity between studies (ie, the true
association between DRD4 polymorphism and NS var-
ies in the population due to unknown causes) but the
range in which the association is likely to vary is
mostly in the range of small effects (d 0.2). Thus,
the reasons for this variability may be very difcult
to detect.
An important question is not whether an effect
exists, because both weak positive and weak negative
associations are likely to exist in the population, but
rather whether the range of likely effects estimated in
the current meta-analysis is meaningful. Specically,
the statistically true variability falls in a range that sug-
gests that most true effects are very weak. For example,
even if we assume, as the data suggest, that in some
conditions the link between presence of long alleles
and NS is about d = 0.16 (Hunter & Schmidt method,
Table 3), or that the correlation coefcient between
presence of long alleles and NS is 0.08, it is question-
Molecular Psychiatry
able whether practically these true effects justify a
search for moderators. Detecting moderators of such a
small effect size statistically requires very large data
sets. However, note that weak statistical effects could
be important but that the judgement is based not on
statistics but on substantive knowledge of meaning of
the effect.
34
For example, if one translates ndings
regarding the association between smoking (yes/no)
and occurrence of a heart attack (yes/no), the d stat-
istics will be roughly 0.14. However, it corresponds to
an odds ratio of 6:1, where 6% of smokers are expected
to suffer from heart attack as opposed to 1% of non-
smokers.
34
In that case, the very small statistical effect
size (most people whether smokers or not will not suf-
fer heart attack) is very meaningful. The meaning-
fulness is independent of effect size. Thus, researchers
in the eld have to assess whether or not variable small
true association between DRD4 and NS is theoretically
meaningful. This may become clearer, perhaps, with
the identication of other genetic correlates of NS.
We, nevertheless, attempted to identify potential
moderators in the data set analyzed in the current
meta-analysis. Four variables that might be contribu-
ting to differences in reports and that were identiable
in the published studies included the mean age of sam-
ple, ethnic groups (European vs others), gender and
clinical characteristics of the sample (alcoholic vs non-
alcoholic). None of the four moderators we analyzed
proved signicant although there was a trend for age
and ethnicity to affect the purported association
between the DRD4 polymorphism and NS. Given the
small number of studies in this meta-analysis (k = 20),
the moderator analysed results must be interpreted
with great caution due to second order sampling
error.
10,35
That is, unlike the estimate of the association
between DRD4 and NS that is based on approximately
4000 observations (high statistical power), the esti-
mates of the moderators are based on 20 samples
(extremely low statistical power).
One potential concern with this meta-analysis is the
comparison of the long vs short allele. First, there is
evidence of sequence variation within particular repeat
lengths that may also play a role in receptor func-
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tioning. At least 35 distinct repeat variant motifs were
observed for the DRD4 gene.
36
The two most common
haplotypes for the 4 and 7 repeat alleles respectively
account for 95% and 89% of the observed sequence
variants.
36
Due to the infrequence of the additional
haplotypes, it seems to us unlikely that they inuenced
our estimates of the association between NS and allelic
type. However, this possibility cannot be excluded and
one particular sequence variant of the 7 or 4 repeat
allele may be responsible for the effect of one or both
of these alleles on NS. Although no information is cur-
rently available concerning possible functional differ-
ences among variant repeats of the same length, it
might be worthwhile to address this issue in future
genetic and physiological studies.
Second, on the basis of a worldwide sample it is
argued that the 7 repeat allele is evolutionarily younger
than the common 4 repeat allele. Furthermore, on the
basis of this report, it is suggested that the 7 repeat
allele is not simply related to other common alleles and
that it has increased to high frequency in humans by
positive selection.
36
Thus, the reports that collapse sev-
eral alleles into one category of long may be missing
important information. However, in our meta-analysis
15 out of the 20 samples compared the specic effect
of 7 repeat presence/absence on NS and yielded practi-
cally the same results (eg, mean d of these 15 studies
is 0.01 and the heterogeneity estimates remain largely
unchanged also). Nevertheless, future research regard-
ing the DRD4 gene should consider these recent nd-
ings regarding the 7 repeat allele.
The failure to nd a moderator is not surprising
given the combination of small number of studies (k)
and small range of effects (all d 1). To discover
unknown moderators, future studies should search for
an interaction between the presence of the long allele
and other factors in affecting NS. These factors may be
either genetic (eg, allelic or locus heterogeneity),
environmental (eg, meaning of NS behavior in different
cultures), or measurement related (eg, NS response
may not be equivalent across cultures and languages).
Perhaps a more fruitful approach towards identifying
factors that truly contribute to the variability in associ-
ation studies between DRD4 and NS would be based
on the highly polymorphic nature of this gene. At least
10 polymorphisms (outside of the repeat region) of the
DRD4 receptor have been described to date and nine
are discussed in a recent review by Paterson et al.
8
The
most recently reported polymorphisms are a group of
SNPs (single nucleotide polymorphisms) in the pro-
moter region, one of which (521 C/T) is observed to
regulate transcription of the receptor.
37
This plethora
of DRD4 receptor region polymorphisms raises the
possibility that the reported association between the
exon III polymorphism and NS is due to linkage dis-
equilibrium between the long repeat and another one
or more of the reported polymorphisms at this locus.
Allelic heterogeneity can create situations in which
multiple different alleles are associated with NS, rather
than a single specic allele. Studying haplotypes can
to some degree overcome hypothetical weak linkage
equilibrium between the 7 allele and a true functional
polymorphism.
38
For example, a haplotype approach
has been used to further analyze the role of the DRD4
receptor in attention decit disorder. Indeed, such an
analysis strengthens the connection between the gene
and the disorder although the relationship between
DRD4 and attention decit is not simple.
39
Additionally, in the case of personality traits locus
heterogeneity is also likely to be present and many
genes dispersed in the genome may be partially con-
tributing to NS. For example, Cloninger et al
40
in a
linkage study of anxiety-related traits has identied a
number of epistatic loci on different chromosomes. We
have provisionally identied two additional functional
polymorphisms that may be contributing to NS.
41
It
should also be noted that in Chinese and Japanese
populations the long repeat alleles, including the 7
repeat, are extremely rare and cannot be contributing
to NS. Indeed, in the Japanese population an associ-
ation has been reported between NS and one of the pro-
moter region polymorphisms.
37
Human personality is a complex phenotype in which
both genetic and environmental factors play a role.
Moreover, similar to other complex traits it is likely
that a number of genes, each yielding a small effect
size, contribute to the phenotype and any one polymor-
phism may neither be necessary nor sufcient to deter-
mine the trait. Since different investigators draw on
diverse populations in studies of personality, the gen-
etic background of these populations likely varies for
common polymorphisms, thus potentially con-
founding the identication of any specic genes of
small effect size that contributes to personality traits.
Validation of a role of polymorphisms in contributing
to a complex trait may well depend on knowledge of
additional genes contributing to this trait, and when
studies are carried out across ethnic groups, on the fre-
quency of these other polymorphisms across popu-
lations. The growing availability of powerful statistical
techniques, high-throughput genotyping and large
numbers of polymorphic markers such as single nucle-
otide polymorphisms makes such proposed studies
increasingly feasible.
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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    • "In recent years, growing evidence has suggested that animal temperaments are partly genetically-determined. For example, polymorphisms at the dopamine receptor D 4 gene (DRD4) are often associated with variation in diverse traits such as fear, novelty seeking and body mass (e.g.252627, but see: [28, 29]). DRD4 is an important component of the dopaminergic system, coding for a subtype of dopamine receptor in vertebrates [30] . "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Interactions between wildlife and humans are increasing. Urban animals are often less wary of humans than their non-urban counterparts, which could be explained by habituation, adaptation or local site selection. Under local site selection, individuals that are less tolerant of humans are less likely to settle in urban areas. However, there is little evidence for such temperament-based site selection, and even less is known about its underlying genetic basis. We tested whether site selection in urban and non-urban habitats by black swans (Cygnus atratus) was associated with polymorphisms in two genes linked to fear in animals, the dopamine receptor D4 (DRD4) and serotonin transporter (SERT) genes. Results: Wariness in swans was highly repeatable between disturbance events (repeatability = 0.61) and non-urban swans initiated escape from humans earlier than urban swans. We found no inter-individual variation in the SERT gene, but identified five DRD4 genotypes and an association between DRD4 genotype and wariness. Individuals possessing the most common DRD4 genotype were less wary than individuals possessing rarer genotypes. As predicted by the local site selection hypothesis, genotypes associated with wary behaviour were over three times more frequent at the non-urban site. This resulted in moderate population differentiation at DRD4 (FST = 0.080), despite the sites being separated by only 30 km, a short distance for this highly-mobile species. Low population differentiation at neutrally-selected microsatellite loci and the likely occasional migration of swans between the populations reduces the likelihood of local site adaptations. Conclusion: Our results suggest that wariness in swans is partly genetically-determined and that wary swans settle in less-disturbed areas. More generally, our findings suggest that site-specific management strategies may be necessary that consider the temperament of local animals.
    Full-text · Article · Dec 2015 · BMC Evolutionary Biology
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    • "The most promising candidate genes for human personality traits are the dopamine receptor D4 (DRD4), involved in the mediation of the hormone dopamine in the dopaminergic system , and the serotonin transporter (SERT), which controls the uptake of the hormone serotonin in the synaptic clefts of the neurones [8]. Although null results have been found in candidate gene association studies [8], variation in novelty-seeking behaviour in humans is generally associated with polymorphisms in DRD4 [9] and low levels of novelty seeking behaviour have been recorded in DRD4 deficient mice [10]. Additionally, variation in measures of anxiety related behaviour in humans has been associated with polymorphisms in SERT [11,12] and high levels of anxiety related behaviour and low levels of novelty seeking have been reported in SERT deficient mice [13,14]. "
    [Show abstract] [Hide abstract] ABSTRACT: Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes.
    Full-text · Article · Oct 2015 · PLoS ONE
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    • "Specially, presence of the seven-repeat variant (i.e., having at least one allele with seven Fam. Proc., Vol. x, xxxx, 2015 HARTMAN & BELSKY / 7 repeats) has been identified as a vulnerability factor due to its links to ADHD (Faraone, Doyle, Mick, & Biederman, 2001), high novelty seeking behavior (Kluger, Siegfried, & Ebstein, 2002), and low dopamine reception efficiency (Robbins & Everitt, 1999), among other correlates. As it turns out, a number of studies indicate that children carrying this putative risk allele are not only more adversely affected by poorer quality parenting than other children , but also benefit more than others from good-quality rearing. "
    [Show abstract] [Hide abstract] ABSTRACT: An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. © 2015 Family Process Institute.
    Full-text · Article · Jul 2015 · Family Process
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