Associations between Oxytocin Receptor (OXTR) Genotype and Elementary School Children’s Likability, Dis-likability and Friendship among Classroom Peers: A Longitudinal Study
Journal of Youth and Adolescence
Associations between Oxytocin Receptor (OXTR) Genotype and Elementary School Children's Likability, Dis-likability and Friendship among Classroom Peers: A Longitudinal Study
Jin He 0 1
● J. Marieke Buil 0 1
● Hans M. Koot 0 1
● Pol A. C. van Lier 0 1
0 Amsterdam Public Health Research Institute , Van der Boechorststraat 7, Amsterdam 1081 BT , The Netherlands
1 Department of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam , Van der Boechorststraat 1, Amsterdam 1081 BT , The Netherlands
The single nucleotide polymorphism rs53576 of the oxytocin receptor (OXTR) gene is involved in forming and maintaining relationships in various social contexts. However, this has not been studied in the childhood peer context. The present study followed 359 children (51.6% girls) from age 9 to 12 to explore associations between OXTR rs53576 genotype (i.e., AA, AG or GG genotype) and three indicators of children's relationships with peers: likability and dis-likability among, and friendship with, classroom peers. Our results showed that OXTR rs53576 was associated with likability among boys, but not with dis-likability and friendship or among girls. Boys with an A and a G allele (i.e., AG genotype) became increasingly more liked by their peers across the four-year studied period than those with two A alleles or two G alleles (i.e., AA and GG genotype). This study indicates that OXTR rs53576 genotype might influence children's peer relationships, particularly their likeability among peers. Associations between OXTR rs53576 and peer relationships may differ depending on children's sex and the specific type of peer-relationship under scrutiny.
Children’s relationships with their classroom peers play an
important role in their social, emotional and behavioral
development during elementary school years
et al. 2002; Choukas-Bradley and Prinstein 2014)
example, children who are not liked by their peers or who
have no or only a few friends are at risk of developing
various social and psychological problems, such as
becoming bullying victims
(Hodges et al. 1999; van Lier
and Koot 2010)
, and developing emotional and behavioral
(Fontaine et al. 2009; Kiesner 2002; Ladd and
. Previous studies have indicated that a
significant part of the differences in children’s peer
relationships might be explained by their genetic makeup
(Boivin et al. 2013; Brendgen et al. 2009)
. One of the genes
implicated in forming and maintaining relationships with
others is the single nucleotide polymorphism rs53576 of the
oxytocin receptor (OXTR) gene. The goal of the present
study is to investigate the potential association between
OXTR rs53576 and children’s relationships with classroom
peers. Specifically, we studied the association between
OXTR rs53576 and children’s likability, dis-likability, and
friendship as perceived by their classmates from ages 9 to
The OXTR gene has been linked to social behaviors that
are important for forming and maintaining social
(e.g., Kogan et al. 2011; Walum et al. 2012)
. One of
the most studied polymorphisms within the OXTR gene is
the single nucleotide polymorphism (SNP) rs53576
(Bakermans-Kranenburg and van IJzendoorn 2014; Li et al.
. Evidence from a wide range of studies, which
together cover the developmental period from infancy to
adulthood, has shown that this SNP is linked to factors
important for building and maintaining social relationships,
such as the cognitive capability to efficiently process social
and emotional information
(Choi et al. 2017; Lucht et al.
2013; Tops et al. 2011)
. Furthermore, OXTR rs52576 has
been associated with social relationships in a broad range of
contexts, such as interactions within the family, romantic
relationships, and interactions with strangers
(BakermansKranenburg and van IJzendoorn 2014; Li et al. 2015)
However, knowledge about the potential role of OXTR
rs52576 genotype in social relationships with peers during
childhood is yet far from complete and several important
questions are still unanswered.
Association between ×OXTR rs53576 and Peer
Whether variation within OXTR rs52576 is associated with
the development of children’s peer relationships is as of
yet unclear. To the best of our knowledge, no previous
studies have investigated the association between OXTR
rs53576 and classroom peer relationships of elementary
school children. Some studies of preschoolers and
elementary school children have found that the rs53576
polymorphism was linked to several characteristics that
may indirectly affect children’s peer relationships. For
example, among three to five-year-old children, OXTR
rs53576 was associated with helping and sharing
(Wu and Su 2015)
, as well as with negativity and
avoidance in the context of social interactions
et al. 2014)
. In ten-year-old children, the polymorphism
was associated with the ability to recognizing human
faces, which is important for social interactions
et al. 2014)
. In addition, among adolescents, a study found
that variations in OXTR rs53576 predicted different
developmental patterns of loneliness across a five-year
(van Roekel et al. 2013)
. Thus, there is
growing evidence indicated that OXTR rs53576 is linked
to personal characteristics and behaviors that may affect
children’s relationships with peers. Yet, studies that
directly focus on the role of OXTR rs52576 in the
peercontext are lacking.
Function of OXTR rs53576 Genotypes
Despite the attention from many studies, it remains unclear
which specific allele of the OXTR rs53576 might be
beneficial for forming and maintaining positive social affiliations
and which allele might be considered ‘risky’, in that it may
hamper the development of positive social bonds. The SNP
rs53576 within the OXTR gene consists of a nucleotide
guanine (G) to adenine (A) change, resulting in three allelic
combinations, or genotypes, namely: AA, AG, and GG
(Gillath et al. 2008)
. Currently, there is no empirical
evidence about how the three OXTR rs53576 genotypes are
associated with oxytocin density and functioning of the
(Gimpl and Fahrenholz, 2001; van
Roekel et al. 2013)
. Because of the lack of biological
evidence, previous studies have inferred its genotype
functioning from neurological, neuroendocrine and the
abovementioned behavioral studies. For example, studies
have detected associations between variants of OXTR
rs53576 and activities of some brain areas
and hypothalamus; Waller et al. 2016; Wang et al. 2014)
and some hormones
(e.g., cortisol; Chen et al. 2011;
McQuaid et al. 2015)
. Nevertheless, without precise
information about how the OXTR rs53576 genotypes are related
to oxytocin density and functioning of the oxytocinergic
system, it is unclear how the genotypes should be coded in
quantitative genetic studies. Possibly as a result of this
uncertainty, previous studies have used different schemes to
code OXTR genotypes when investigating its association
with social outcomes.
Previous studies have used three different schemes of
coding the OXTR rs53576 genotypes. The first scheme
grouped individuals with an A allele (i.e., AA and AG
genotypes) together, and contrasted this AA/AG group with
people carrying GG genotype. This A-dominant model is
based on the assumption that when both the A and G allele
are present, only the A allele would be expressed and affect
phenotypes. This coding scheme has resulted in inconsistent
findings. Some studies found that GG carriers showed more
comforting and sharing behaviors
(Wu and Su 2015)
(Kogan et al. 2011; Krueger et al. 2012)
more social empathy
(Gong et al. 2017; Rodrigues et al.
, and better cognitive capability in processing visual
and auditory information during social interactions
et al. 2011; Verhagen et al. 2014)
, compared to individuals
with an AA/AG genotype. Other studies found that AA/AG
carriers, and not the GG carriers, exhibited good emotion
recognition skills (Lucht et al. 2009), showed decreasing
loneliness over time
(van Roekel et al. 2013)
experienced less separation anxiety (Costa et al. 2009).
In the second group of studies, individuals with a G allele
(i.e., GG and AG genotypes) are compared with individuals
without a G allele (i.e., the AA genotype). This G-dominant
coding scheme implicates that when both the A and G
alleles are present, only the G allele would be expressed and
affect phenotypes. Studies that used this scheme have also
yielded conflicting results. One study found that the AA
genotype was associated with more negative emotionality
(Kryski et al. 2014)
compared to the AG/GG genotype.
However, other studies found that AA carriers scored better
(i.e., lower) in a social impairment test
(Park et al. 2010;
Slane et al. 2014)
and showed better emotion recognition
skills for both positive and negative emotions (Lucht et al.
2009) than GG/AG carriers.
The third genotype-coding scheme considered the three
allelic combinations AA, AG, and GG as three different
groups and that the frequency of one of the alleles (A or G
allele for OXTR rs53576) would influence a particular
phenotype. For instance, if the strength of the association
between OXTR rs53576 GG genotype and peer relationship
would be represented by a parameter γ, then the strength
increases γ-fold for genotype AG and by 2γ-fold for
(Clarke et al. 2011)
. In other words, the
association between allele frequency and a particular phenotype
is linear in nature. Using this additive model, Lucht and
colleagues (2009) found level differences in positive affect
across the three genotypes. Specifically, the AA genotype
carriers had the lowest levels of positive affect, GG carriers
with the highest levels of positive affect, and AG carriers
with in-between levels of positive affect. However, other
studies using this approach found no relationship between
the three genotypes and indicators of social affiliation
attachment, Chen and Johnson 2012)
, social cognition (e.g.,
face recognition memory; Skuse et al. 2014), and emotional
reactions or behaviors in a social context
(e.g., sharing and
trust; Apicella et al. 2010; Tabak et al. 2014)
One drawback of previous studies is that one coding
scheme – the heterotic model − has not been considered,
whereas the link between OXTR rs53576 and social
relationships might also be heterotic. Genetic heterosis occurs
when individuals with a heterozygote of a specific genetic
polymorphism (i.e., two different alleles; AG in the present
study) show different levels of a phenotype than individuals
(i.e., two identical alleles; AA and GG in
the present study; Comings and MacMurray 2000)
Although this coding model has, to our knowledge, not
been used to study the OXTR gene in humans, a review of
molecular heterosis revealed that genetic heterosis is
common in humans and may be prevalent in up to 50% of all
. Without the certainty of the biological
functioning of the OXTR rs53576 genotypes, a heterosis effect
of OXTR rs53576 on social affiliations cannot be ruled out.
Evidence of heterosis among human studies has been
discovered for the catechol O-methyltransferase receptor
(COMT) gene, the dopamine receptor D2 (DRD2) gene, and
the serotonin transporter gene
(SLC6A4; Costas et al. 2011;
Coutinho et al. 2004; Gelernter et al. 1993; Gosso et al.
2008; Middeldorp et al. 2007)
. For example, one study
found that infants with heterozygotic genotypes of the
COMT polymorphism had higher levels of attachment
(Luijk et al. 2011)
, compared to their homozygotic
Comings and MacMurray (2000)
found that some of the heterotic genotype-phenotype
associations were blurred when using inaccurate coding scheme.
This might also explain why the results of OXTR rs53576
and its association with social-relationship phenotypes are
(e.g., Bakermans-Kranenburg and van
IJzendoorn 2014; Li et al. 2015)
, because the link between OXTR
rs53576 and social relationships might also be heterotic and
were potentially blurred when the genotypes were not coded
In the present study, we therefore explored the modeling
rs53576 genotypes with the four different genotype-coding
schemes (i.e., an A-dominant model, a G-dominant model,
an additive model, and a heterotic model) to investigate
which specific allele underlies the association between
OXTR rs53576 and the three indicators of children’s peer
relationships of interest.
Sex Difference of the OXTR-Peer Relationship
Another question about effects of OXTR rs53576 is whether
the potential associations between variants of OXTR
rs53576 and children’s peer relationships may be
sexspecific. Findings concerning sex differences in social
outcomes linked to the SNP are inconsistent. Some previous
studies found that the associations between OXTR
polymorphism and, for example, prosocial behavior, were
stronger among males, compared to females
et al. 2011)
. Similarly, another study found that the
association between OXTR and trust behavior
(Krueger et al.
was significant only for males and not for females. In
contrast, several other studies found significant OXTR
effects for females but not for males, for example, on
(van Roekel et al. 2013; van Roekel et al. 2013)
In contrast to these findings, there are also studies that did
not find significant differences between males and females
(e.g., Lucht et al. 2013)
, while other studies, especially
some studies in childhood, did not consider sex differences
(e.g., Slane et al. 2014; Wu and Su 2015)
. Based on these
findings, sex differences in the association between OXTR
rs53576 and peer relationships cannot be ruled out and,
therefore, were investigated in the present study.
The goal of the present study was to investigate whether
OXTR rs53576 would be associated with children’s peer
relationships in the context of their elementary school
classroom. We included three indicators of peer
relationships as the outcome: likability, dis-likability, and
friendship as perceived by classroom peers. We tested the effects
of the OXTR gene with four different genotype-coding
models in order to explore whether the potential
genotypephenotype associations would be affected by the way that
alleles were coded. In addition, possible sex differences in
the OXTR-peer relationship associations were also
examined for each genotype-coding scheme and for each peer
relationship outcome. Given the lack of studies on the
association of the OXTR gene with peer relationships and
the mixed results of previous studies on social outcomes,
we formulated no a priori hypotheses.
Data of the present study (359 children, 48.4% boys) came
from two longitudinal studies assessing children’s social,
emotional and behavioral development across the
elementary school years. In the first project, schools in the west and
east of the Netherlands were invited to participate, and the
first 30 schools that accepted this invitation were included
in the project. At the beginning of the first project, parental
informed consent was obtained for 90% of the schools’
children who were invited
(Menting et al. 2011)
. In the
second project, 18 schools from the north and east of the
Netherlands were recruited through municipal health
services. Parental informed consent was obtained for almost all
(99.9%; Gooren et al. 2011)
. The projects were
reviewed by the medical ethics boards of the Erasmus
Medical Center Rotterdam and the Vrije Universiteit
Medical Center Amsterdam. Children were assessed annually
during their elementary school years. In the first and second
grades, a classroom-based preventive intervention program
targeting behavioral problems
(either the Good Behavior
Game; Dolan et al. 1989; Van der Sar and Goudswaard
2001; or the Promoting Alternative Thinking Strategies
curriculum, Kusché and Greenberg 1994)
implemented. Schools were randomly assigned to the intervention
or the control condition. We oversampled children in the
intervention condition so that approximately 60% of the
children were in the intervention condition. After the second
grade, all schools could decide whether or not to implement
the intervention programs and the implementation was no
longer monitored by the research team. Data from children
in the third to sixth grade (from 9 to 12 years old, four
assessments) were used in the present study. Given that the
years included in the present study were out of the planned
intervention period, we did not expect intervention effects
on the studied associations. Nevertheless, possible
intervention effects on all studied associations were tested.
All children who participated and remained in the final
assessment of the longitudinal projects (N = 1091) were
invited to provide a saliva sample for DNA extraction at age
13. Of those, a total of 406 children provided saliva samples
and OXTR rs53576 genotype was subtracted successfully
for 400 children. Among them, 41 children had no peer
relationship data on the waves included in the present study
(the 3rd–6th grade), and hence were not included. As a
result, data from a total of 359 children (48.4% boys) were
included in the analyses. Of these children, 40 children had
an AA genotype (21 boys; 52.5%), 164 had an AG
genotype (83 boys; 50.6%) and 155 had a GG genotype (70
boys; 45.2%). The distribution of genotypes in the present
sample was equal to the Hardy-Weinberg Equilibrium
expectations (χ2(2) = .02, p = .99) in the European
population. The majority of the participants (90.6%) were of the
Dutch/Caucasian descent. Two point four percent (2.4%) of
the included children were Moroccan; 1.2% Surinamese;
0.9% Turkish; and 2.1% of children belonged to other
ethnic groups; 2.8 % had missing data on ethnicity. Of all
children who were invited to provide saliva samples,
children who did not consent to saliva collection did not differ
from those who did on friendship (F (1, 820) = 0.31,
p = .58), but scored higher on peer likability (F (1, 820) =
6.40, p = .01) and lower on peer dis-likability (F (1, 820) =
14.17, p < .001). Among children who provided a saliva
sample, those who did not have peer relationship data on the
waves included in the present study (N = 41) did not
significantly differ on OXTR genotype distribution (χ2(2)
= .46, p = .80), sex (χ2(1) = .11, p = .74), or intervention
condition (χ2(1) = .41, p = .52) compared to children who
had peer relationship data.
Schools were contacted through phone calls. The purpose
and procedure of the projects were explained to the school
principles. After the school principals granted permission, a
letter that explained the procedures and measurements and a
consent form were sent to the children’s parents. Only
children with written parental consent participated in the
study. Peer relationship data of the present study were
collected during regular classroom hours in the classroom.
Children were arranged to sit separately in order to assure
privacy and were instructed not to talk with their classmates
about the questionnaires. After the general instruction,
children received a list with the names of all classmates who
were granted consent to participate in the study. Children
were instructed to nominate classmates (by checking
classmates’ names) that fitted the description provided on
top of the paper (e.g., who do you like most). After the
measurements, children were offered a small gift as a token
for their participation.
Written consent forms for the DNA study were sent
through post to the parents of the children, and the children
themselves if they were older than 12 years old.
Saliva samples were collected using the OrageneTM DNA
Self-Collection Kit (OG-500 tube) according to the
instruction of the manufacturer (DNAGenotek, Ottawa,
Ontario, CAN). The self-collection kit consists of a tube in
which children have to spit 2 ml of saliva (until the ‘fill line’
on the tube). The children were instructed not to eat, drink
(except for water), smoke or chew gum 30 min before the
saliva collection. Detailed instructions can be found at the
manufacturer’s website (http://www.dnagenotek.com/
ROW/pdf/PD-BR-017.pdf). Trained research assistants
assisted the participants with collecting saliva at the
participants’ homes and ensured that the children followed the
OXTR rs53576 genotypes
OXTR rs53576 genotypes were subtracted from saliva
samples. The polymorphism of OXTR rs53576 was
genotyped using PCR and fragment analysis on a 3130 Genetic
Analyzer (Life Technologies, Carlsbad, CA). Coding of
genotypes varied according to the schemes: in the
Adominant model, AA and AG were combined and coded as
0, while GG was coded as 1; in the G-dominant model, AA
was coded as 0, while AG and GG were combined and
coded as 1; in the additive model, AA was coded as −1, AG
as 0 and GG as 1; and in the heterotic model, AA and GG
were combined and coded as 0, while AG was coded as 1.
participated in the nomination procedure minus one,
resulting in scores ranging from 0 to 1. Higher scores
indicate that the child was perceived as a friend by more
Children’s sex was dummy coded as 0 (girls) and 1 (boys).
Principal coordinates for population stratification
Three constructs were included to control for possible
confounding effects of population stratification on the effect
of OXTR genotype. Children’s ethnicity represented
approximately the global level of population stratification,
coded as 1 (Dutch and Western immigrants, 90.6% of the
sample) and 0 (other ethnicities). The local level of
population stratification were represented approximately by two
positional variables (North/South and East/West) of the
children’s residential location according to a genome-wide
study about the population structure in the Netherlands
(Abdellaoui et al. 2013)
. The residences of children who
participated in the present study were in three areas and
were dummy coded as 1 (North) and 0 (South) for the
North/South dimension and 1 (East) and 0 (West) for the
Peer likability and peer dis-likability
Intervention status of children
Peer likability and dis-likability were assessed annually
based on the protocol described by
Coie and Kupersmidt
. Children were asked to nominate an unlimited
number of classmates who they liked most and classmates
who they liked least. For each child, the ‘liked most’ and
‘liked least’ nominations were divided by the number of
children who participated in the nomination procedure from
the same classroom minus one (children were not allowed
to nominate themselves). This resulted in scores ranging
from 0 to 1. For likability, higher scores indicate being liked
more. For dis-likability, higher scores indicate being
disliked more by peers.
Friendship was assessed annually by asking children to
nominate an unlimited number of classmates whom they
considered as their friends. Because our focus was on how
the target child was perceived by their classmates,
unidirectional friendship nominations (i.e., a classmate
nominated the target child as a friend, but the target child did not
necessarily nominate this particular classmate back as a
friend) were used in the analyses. The nominations each
child received were divided by the number of children who
Intervention status at first and second grade was dummy
coded as 0 (control) and 1 (intervention).
Household socioeconomic status
Household socioeconomic status (SES) was assessed
through children’s parental occupational status based on the
Dutch Working Population Classification of Occupations
(Statistics Netherlands 2017)
. The highest
occupational level of the parent(s) was chosen to represent
children’s household SES. Household SES was coded as 1
(unemployed to lower SES) and 0 (medium to higher SES)
for each child.
Associations between OXTR rs53576 genotypes and peer
relationships were estimated through latent growth curve
(LGCM, Muthén and Khoo 1998; see Fig.1)
LGCMs were fitted separately for the three peer relationship
outcomes (i.e., peer likability, peer dis-likability, and
friendship). LGCMs estimate two growth parameters for
each outcome: the level of the peer relationship outcome,
represented by an intercept, and the developmental trend of
the outcome across the whole studied period (i.e., from age
9 to 12 years), represented by a linear slope. The intercept
was centered at the age of 11 years to estimate the level of
peer relationships in the middle of the covered period. Paths
from OXTR rs53576 genotype to both parameters were
modeled to represent OXTR-peer relationship associations.
The analyses were performed in two steps. In the first
step, we used model fit indices of the LGCMs to select the
genotype-coding model that fitted the best for OXTR-peer
relationships associations and to estimate sex differences in
the associations. To estimate the best fit genotype-coding
model, we compared the model fit indices that are allowed
for non-nested model comparisons
(Curran et al. 2010;
Widaman and Thompson 2003)
of models with OXTR
genotype being coded according to four different models:
the A-dominant model, the G-dominant model, the additive
model, and the heterotic model. The model fit indices for
non-nested model comparisons included Akaike’s
information criterion (AIC; Akaike 1998), the Bayesian
(BIC; Schwarz 1978)
, and the sample-size
adjusted Bayesian information criterion
. For all three model-fit indices, smaller values
indicate better fit. To estimate sex differences in the OXTR-peer
relationship associations, the LGCMs were fitted with
multiple group comparisons (boys vs. girls), in which the fit
of a model with sex-specific estimates was compared to the
fit of a model in which effects were held equal across sex
(sex-equal model). Changes in chi-squares of the two
models were tested using the Satorra-Bentler test
, with a significant change indicating sex
After the best fit genotype-coding model and sex model
were selected, we performed the second step of our
analysis, in which the associations between OXTR genotypes and
the peer relationship outcomes were estimated. The LGCMs
were estimated for each peer relationship outcome
separately. The association between OXTR rs53576 genotypes
and the peer relationship outcomes (i.e., either likability,
dis-likability or friendship) was estimated first without
covariates (basic model), then with the covariance between
the target outcome and other indicators of peer relationship,
by including one of the other two indicators of peer
relationship as a time-varying covariate (covariate model; see
Children’s household socioeconomic status, intervention
status, and the principal coordinates for population
stratification (i.e., ethnicity and area of residence) were controlled
as predictors of the phenotype growth parameters in all
latent growth curve models. Moreover, intervention status
was also tested as a moderator on all genotype-phenotype
associations, to see whether the intervention affected the
studied associations. Models were fitted using the software
Mplus 7.31 (
Muthén and Muthén 1998
errors of all paths were adjusted for clustering of data within
classrooms using a sandwich estimator
Maximum likelihood estimation with robust standard errors
(MLR) was used in order to account for the non-normal
distributions of dis-likability and friendship. Missing data
were handled with the full information maximum likelihood
Descriptive statistics are reported in Table 1. Repeated
ANOVAs showed that boys scored lower than girls on peer
likability but higher on peer dis-likability. No sex difference
for level of friendship was found. All correlations (see
Table 2) between the studied variables were in the expected
direction. Furthermore, the slope parameters of peer
likability (slope = .02, SE = .01, p = .22), peer dis-likability
(slope = −.01, SE < .01, p = .06), and friendship (slope
= .01, SE < .01, p = .18) indicate that on average, the
number of peer-nominations that children received for
likability, dis-likability and friendship were stable from 9 to 12
years of age.
Associations Between OXTR rs53576 and Peer
Likability, Dis-likability and Friendship
We first estimated models for the association between
OXTR rs53576 and peer likability. Model fit results showed
that the sex-specific heterotic model had the best fit
according to the AIC and aBIC fit indices, while the
sexequal A-dominant model showed the best fit according to
BIC (in Table 3). However, the SB test showed a significant
sex difference for the A-dominant model. Therefore, we
rejected the sex-equal A-dominant model and select the
sexspecific heterotic model as the best fit model. We then tested
intervention effects by adding intervention status as a
moderator on the association between OXTR genotype and
peer likability. The three-way interaction (i.e., sex ×
intervention status × OXTR genotype) was not significant
(intercept: B = −.01, SE = .06, p = .86; slope: B = −.03,
SE = .02, p = .23). Thus, invention status was then
controlled by including it in the models as a covariate in the
prediction of the growth parameters of likability.
The model estimates (see Table 4) show that in the basic
model, the associations between genotype and the intercept,
as well as the slope of likability, was significant for boys,
but not for girls. Specifically, boys with an AG genotype
had higher level (i.e., intercept) and a significant increase
(i.e., slope) of likability during the length of the study
compared to boys with either an AA or a GG genotype. No
association between OXTR genotype and likability was
found for girls. When peer dis-likability was added to the
model as a time-varying covariate, the association between
All correlations in the table are significant (p < .001)
Δχ2 statistics are based on the Satorra-Bentler Chi square difference
test. The genotype-coding model chosen for each peer relationship
indicator are marked bold
*p < .05, **p < .01, ***p < .001
OXTR and the growth parameters remained significant.
However, when friendship was added as a covariate, the
association between OXTR genotype and the intercept
of peer likeability was no longer significant, while the
association with the slope of peer likability remained
Model fit results (see Table 3) showed that the sex-specific
heterotic model fitted the data best according to AIC and
aBIC values, while the sex-equal heterotic model showed
the best fit according to BIC. However, SB test showed
significant sex differences for all genetic models. Thus, the
sex-specific heterotic model was chosen as the best fit
model. Again, we tested for potential intervention effects.
The three-way interaction (i.e., sex × intervention status ×
OXTR genotype) was not significant (intercept: B = .04, SE
= .05, p = .48; slope: B < .01, SE = .02, p = .93). Invention
status was therefore controlled by including it in the models
as a covariate.
Results in Table 5 show a significant effect of genotype
on the intercept of peer dis-likability for boys only in the
basic model. No significant association between OXTR
genotype and the slope of dis-likability was found. Also, no
association between OXTR genotype and dis-likability
(intercept or slope) was found for girls. Moreover, after
including peer likability or friendship as time-varying
covariates, the association between peer dis-likability and
OXTR genotype was no longer statistically significant,
indicating that the OXTR-peer dis-likability association
might be explained by the associations between the
genotype and peer likeability or friendship.
Model fit results (in Table 3) showed the that the
sexspecific heterotic model was the best fitting model
according to the AIC, but the BIC and aBIC indicated that the
sexequal A-dominant model had the best fit. SB test also
showed conflicting results, with significant sex differences
for the heterotic model, but no significant sex difference for
A-dominant model. The sex-equal A-dominant model was
preferred by two out of three model indices (i.e., BIC and
aBIC) and the other (i.e., AIC) had a value very close to the
best fit value (AIC of sex-specific heterotic model).
Therefore, the sex-equal A-dominant model represented the
OXTR-friendship association best. Testing for potential
moderation by intervention yielded no significant results
(intercept: B = −.03, SE = .03, p = .40; slope: B = −.01,
SE = .01, p = .51). Sex and invention status were controlled
as covariates in the model.
Results of the basic model in Table 6 show a significant
association between OXTR genotype with the A-dominant
model and the intercept of friendship, suggesting that
children with an AA or AG genotype were more often
nominated as a friend than those with a GG genotype. No
significant association between OXTR genotype and the
slope of friendship was found. After including peer
likability in the model as a time-varying covariate, the
association between genotype and the intercept of
friendship became non-significant; whereas it remained
significant when peer dis-likability was the covariate. Our
findings indicate that the OXTR-friendship association
overlaps with OXTR-peer likability association.
Previous studies have found that the single nucleotide
polymorphism rs53576 of the oxytocin receptor (OXTR) gene
was associated with various behavioral and social-cognitive
characteristics that are important for forming and maintaining
interpersonal relationships. However, the influence of this
polymorphism on the development of peer relationships in
childhood was unknown. Moreover, previous studies used
different genotype coding schemes to investigate the
influence of the three OXTR genotypes (i.e., AA, AG, and GG) on
social relationships and found inconsistent results. Finally,
whether the effect of OXTR rs53576 varies across sexes was
unclear. Thus, the present study investigated the association
of OXTR rs53576 with three indicators of children’s peer
relationships – likability and dis-likability, and friendship –
among 359 elementary school children followed annually
from age 9 to 12 years. Moreover, we took all possible
genotype coding models into account and investigated the
effect of OXTR genotype on children’s peer relationships
while taking into account potential overlap between the three
peer relationship outcomes.
With this explorative approach, we found that the OXTR
rs53576 polymorphism, in general, was associated with the
development of children’s peer relationships. However, the
specific associations differed across the peer relationship
outcomes and sex. We found that the association between
OXTR genotype and peer likability remained significant
when the overlap with the other two peer relationship
outcomes (i.e., dis-likability and friendship) was taken into
account. However, the associations between OXTR
genotype and dis-likability and between OXTR and friendship
dropped from significant to non-significant after we
controlled their covariance with likability. This indicates that
the association between OXTR rs53576 genotype and
children’s peer relationships is mainly driven by peer likability,
instead of by dis-likability or friendship. Furthermore, we
found that the association of OXTR genotype with the
development of peer likability was significant only for boys,
and not for girls. Specifically, boys with an AG genotype
became increasingly more liked by classmates from age 9 to
12 years, compared to boys with AA or GG genotype.
Previous research has shown that OXTR genotype is
associated with social behaviors within the family or in
interaction with strangers
(Feldman et al. 2012; Krueger
et al. 2012)
. The present study extends our knowledge of
OXTR genotype effect into context of classroom. Moreover,
we found that the magnitude of the association between
OXTR genotype and dis-likability, as well as the association
between OXTR genotype and friendship, were weakened
when the effect of likability was taken into account. This
indicates that peer likability might be the main aspect of
children’s peer relationship that is associated with OXTR
rs53576. Some previous studies also investigated the
association of OXTR genotypes with multiple
(e.g., Lucht et al. 2009; Chen and
. However, these studies did not consider the
potential interconnections between them. Our findings
indicate the importance of taking potential overlap between
different phenotypes into account when investigating the
role of OXTR rs53576.
Regarding the question about how the three OXTR
rs53576 genotypes should be coded when investigating the
association between OXTR rs53576 and peer relationship
phenotypes, our results are inconclusive. We found support
for the heterotic model when peer likability and
dislikability were the outcomes, while for friendship it was the
A-dominant model that fitted the data best. However, no
previous studies have considered the heterotic model when
investigating the effect of OXTR rs53576 on the
development of social relationships. Our findings warrant further
investigation of the heterotic genotype-coding model when
studying associations between OXTR and phenotypes. In
addition, our finding that different coding schemes showed
the best fit to the data dependent on which specific peer
relationship was investigated also suggests that the effect of
OXTR rs53576 on peer relationship might differ for specific
aspects of relationship. Furthermore, we also found that
association between OXTR genotype and friendship was
weakened when likability was taken into account. This
might suggest that the genotype-coding model of the OXTR
rs53576 in association with likability (i.e., the heterotic
model) might outweigh the model of this SNP in association
with friendship. Therefore, the heterotic model might be the
best genotype-coding model to describe the associations
between OXTR genotype and children’s peer relationships.
Our findings, although cannot provide a definite answer
about the correct genotype-coding scheme for OXTR
rs53576, suggest that more caution on genotype coding is
required and that all schemes need to be considered in
future investigations, especially given the lack of
knowledge about OXTR polymorphism functioning.
Regarding the potential gender differences in OXTR-peer
relationship associations, we found that the association of
OXTR rs53576 with peer likability existed only for boys.
This may be due to the different social norms or
expectations that exist for boys and girls. Previous research has
indicated that when both boys and girls showed higher
oxytocin-related socio-emotional competence, such as
(Gong et al. 2017; Rodrigues et al. 2009)
Empathetic boys might be more ‘visible’ to peers than empathetic
girls because empathetic behavior is less expected from
boys compared to girls (Rose and Rudolph 2006). As a
result, boys might particularly benefit from a genotype that
stimulates positive social relationships.
Several limitations should be noted when interpreting our
findings. First, the present study investigated only one SNP
of the OXTR gene. There is growing evidence that other
SNPs of the OXTR gene and SNPs of other genes may be
associated with social competence as well
(DiLalla et al.
2015; Poulin et al. 2012)
. Future studies need to consider
other SNPs or use a genome-wide approach to provide more
comprehensive information about the genetic influence on
children’s peer relationships. Second, it is uncertain whether
our findings can be extended to a larger population.
Although our sample was comprised of children from
mainstream elementary schools, children from minority
ethnicities (9.4%) were under-represented in the present
study (the nationwide rate is around 20% among children
aged from 9 to 12; Statistics Netherlands 2017). Those
children who did not participate our longitudinal projects
might also experience more problems in peer relationships,
which might indicate selective attrition hence hampering
generalizability. In addition, although we controlled for the
potential effect of population stratification with three
approximate constructs, we did not have enough SNPs to
generate principal coordinates specific to our sample. Thus,
we cannot completely exclude the effect of systematic
ancestry differences in the genetic makeup of the children in
our study. Lastly, the peer relationship phenotypes assessed
in the present study were limited to those within children’s
classroom context. Children might have relationships with
peers from other classes or outside school, which were not
covered by our study.
Overall, the present study suggests that OXTR rs53576
genotype is associated with the development of peer
likability in boys from age 9 to 12 years. Boys with an AG
genotype became increasingly more liked among their peers
compared to boys with other genotypes (i.e., AA or GG).
Moreover, peer likability might be the main aspect of
children’s peer relationship (relative to dis-likability and
friendship) that might be associated with OXTR rs53576.
Future studies should consider all potential genotype-coding
models and the role of sex, as well as include multiple
relationship phenotypes and the potential overlap between
phenotypes, to provide more comprehensive knowledge
about the effect of the OXTR gene on social relationships.
Acknowledgements We would like to thank Tuong-Van Vu (Vrije
Universiteit Amsterdam, Department of Clinical, Neuro and
Developmental Psychology) for editing our manuscript. We gratefully
acknowledge the contribution of the participating children and their
Authors’ Contributions J.H. conceived of the study, participated in its
design, drafted the manuscript, performed the statistical analysis and
the main interpretation of the data; J.M.B. conceived of the study,
participated in its design and coordination, participated in
interpretation of the data, and extensively reviewed the manuscript; H.M.K.
conceived of the study, participated in its design and coordination,
participated in interpretation of the data and reviewed the manuscript;
P.A.C. v L. is the PI of both research projects that were included in this
study. He conceived of the study, participated in its design and
coordination, participated in interpretation of the data, and extensively
reviewed the manuscript. All authors approved the final manuscript.
Funding This study was financially supported by the Netherlands
Organization for Health Research and Development (ZonMw) Grants
#26200002 and #50-50110-96-514 and the Chinese Scholarship
Council Grant #201404910559.
Data Sharing Declaration The datasets analyzed during the current
study are not publicly available but are available from the last author
(Pol A. C. van Lier, ) on reasonable request.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflict of
Ethical Approval The medical ethics review boards of the Erasmus
Medical Center Rotterdam and the Vrije Universiteit Medical Center
Amsterdam approved the projects. All procedures followed were in
accordance with the ethical standards of the responsible committee on
human experimentation (institutional and national) and with the
Helsinki Declaration of 1975, as revised in 2000.
Informed Consent Signed informed consent from parents or/and from
children was obtained from all individuals for being included in the
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://crea
tivecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
Jin He M.Sc. is a Ph.D. student at Vrije Universiteit Amsterdam. Her
major research interests include: protective factors and mechanisms of
emotional and behavioral problems in childhood, emotional and
behavioral development, and peer relationships.
J. Marieke Buil Ph.D. is a postdoctoral researcher at Vrije Universiteit
Amsterdam. Her major research interests include: emotional and
behavioral development, peer relationships, DNA and DNA
methylation, bullying prevention/intervention and longitudinal
Hans M. Koot Ph.D. is a Professor emeritus at Vrije Universiteit
Amsterdam. His major research interests include: emotional and
behavioral development, behavioral and emotional problems,
developmental psychopathology, delinquency, quality of life,
intellectual disability, epidemiology, longitudinal research, and
Pol A. C. van Lier Ph.D. is Professor at Vrije Universiteit Amsterdam.
His major research interests include: peer relations, emotional and
behavioral development, behavioral and emotional problems,
psychopathology, delinquency, longitudinal research, and prevention.
Abdellaoui , A. , Hottenga , J. J. , de Knijff, P. , Nivard , M. G. , Xiao , X. , Scheet , P. , & Hudziak , J. J. ( 2013 ). Population structure, migration, and diversifying selection in the Netherlands . European Journal of Human Genetics , 21 ( 11 ), 1277 https://doi.org/ 10.1038/ejhg. 2013 . 48 .
Akaike , H. ( 1998 ). Information theory and an extension of the maximum likelihood principle . In Selected papers of Hirotugu Akaike (pp. 199 - 213 ). Springer, New York, NY. https://doi.org/10.1007/ 978-1- 4612 -1694-0_ 15
Apicella , C. L. , Cesarini , D. , Johannesson , M. , Dawes , C. T. , Lichtenstein , P. , Wallace , B. , et al. ( 2010 ). No association between oxytocin receptor (OXTR) gene polymorphisms and experimentally elicited social preferences . PLoS One . https://doi.org/10. 1371/journal.pone.0011153
Bakermans-Kranenburg , M. J. , & van IJzendoorn, H. M. ( 2008 ). Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting . Social Cognitive and Affective Neuroscience , 3 ( 2 ), 128 - 134 . https://doi.org/10.1093/ scan/nsn004.
Bakermans-Kranenburg , M. J. , & van IJzendoorn, M. H. ( 2014 ). A sociability gene? Meta-analysis of oxytocin receptor genotype effects in humans . Psychiatric Genetics , 24 ( 2 ), 45 - 51 . https://doi. org/10.1097/YPG.0b013e3283643684.
Boivin , M. , Brendgen , M. , Vitaro , F. , Dionne , G. , Girard , A. , Pérusse , D. , & Tremblay , R. E. ( 2013 ). Strong genetic contribution to peer relationship difficulties at school entry: Findings from a longitudinal twin study . Child Development , 84 ( 3 ), 1098 - 1114 . https://doi.org/10.1111/cdev.12019.
Brendgen , M. , Vitaro , F. , Boivin , M. , Girard , A. , Bukowski , W. M. , & Dionne , G. , et al. ( 2009 ). Gene-environment interplay between peer rejection and depressive behavior in children . Journal of Child Psychology and Psychiatry , 50 ( 8 ), 1009 - 1017 . https://doi. org/10.1111/j.1469- 7610 . 2009 . 02052 .x.
Brendgen , M. , Vitaro , F. , Turgeon , L. , & Poulin , F. ( 2002 ). Assessing aggressive and depressed children's social relations with classmates and friends: a matter of perspective . Journal of Abnormal Child Psychology , 30 ( 6 ), 609 - 624 . https://doi.org/10.1023/A: 1020863730902 .
Chen , F. S. , & Johnson , S. C. ( 2012 ). An oxytocin receptor gene variant predicts attachment anxiety in females and autismspectrum traits in males . Social Psychological and Personality Science , 3 ( 1 ), 93 - 99 . https://doi.org/10.1177/1948550611410325.
Chen , F. S. , Kumsta , R., von Dawans , B. , Monakhov , M. , Ebstein , R. P. , & Heinrichs , M. ( 2011 ). Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans . Proceedings of the National Academy of Sciences , 108 ( 50 ), 19937 - 19942 . https://doi.org/10.1073/pnas.1113079108
Choi , D. , Minote , N. , & Watanuki , S. ( 2017 ). Associations between the oxytocin receptor gene (OXTR)rs53576 polymorphism and emotional processing of social and nonsocial cues: An eventrelated potential (ERP) study . Journal of Physiological Anthropology , 36 ( 1 ), 12 https://doi.org/10.1186/s40101-016-0125-3.
Choukas-Bradley , S. , & Prinstein , M. J. ( 2014 ). Peer relationships and the development of psychopathology . In M. Lewis & K. D. Rudolph (Eds.), Handbook of developmental psychopathology (pp. 185 - 204 ). Boston, MA: Springer.
Clarke , G. M. , Anderson , C. A. , Pettersson , F. H. , Cardon , L. R. , Morris , A. P. , & Zondervan , K. T. ( 2011 ). Basic statistical analysis in genetic case-control studies . Nature Protocols , 6 ( 2 ), 121 - 133 . https://doi.org/10.1038/nprot. 2010 . 182 .
Coie , J. D. , & Kupersmidt , J. B. ( 1983 ). A behavioral analysis of emerging social status in Boys' groups . Child Development , 54 ( 6 ), 1400 - 1416 .
Comings , D. E. , & MacMurray , J. P. ( 2000 ). Molecular heterosis: a review . Molecular Genetics and Metabolism , 71 ( 1 ), 19 - 31 . https://doi.org/10.1006/mgme. 2000 . 3015 .
Costa , B. , Pini , S. , Gabelloni , P. , Abelli , M. , Lari , L. , & Cardini , A. , et al. ( 2009 ). Oxytocin receptor polymorphisms and adult attachment style in patients with depression . Psychoneuroendocrinology , 34 ( 10 ), 1506 - 1514 . https://doi.org/10.1016/j. psyneuen. 2009 . 05 .006.
Costas , J. , Sanjuán , J. , Ramos-Ríos , R. , Paz , E. , Agra , S. , & Ivorra , J. L. , et al. ( 2011 ). Heterozygosity at catechol-O-methyltransferase Val158Met and schizophrenia: New data and meta-analysis . Journal of Psychiatric Research , 45 ( 1 ), 7 - 14 . https://doi.org/10. 1016/j.jpsychires. 2010 . 04 .021.
Coutinho , A. M. , Oliveira , G. , Morgadinho , T. , Fesel , C. , Macedo , T. R. , & Bento , C. , et al. ( 2004 ). Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism . Molecular Psychiatry , 9 ( 3 ), 264 - 271 . https:// doi.org/10.1038/sj.mp. 4001409 .
Curran , P. J. , Obeidat , K. , & Losardo , D. ( 2010 ). Twelve frequently asked questions about growth curve modeling . Journal of cognition and Development: Official Journal of the Cognitive Development Society , 11 ( 2 ), 121 - 136 . https://doi.org/10.1080/ 15248371003699969.
DiLalla , L. F. , Bersted , K. , & John , S. G. ( 2015 ). Evidence of reactive gene-environment correlation in preschoolers' prosocial play with unfamiliar peers . Developmental Psychology , 51 ( 10 ), 1464 - 1475 . https://doi.org/10.1037/dev0000047.
Dolan , L. J. , Jaylan , T. , Werthamer , L. , & Kellam , S. ( 1989 ). The Good Behavior Game Manual .. Baltimore , MD: Johns Hopkins Prevention Research Center.
Feldman , R. , Zagoory-Sharon , O. , Weisman , O. , Schneiderman , I. , Gordon , I. , & Maoz , R. , et al. ( 2012 ). Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes . Biological Psychiatry , 72 ( 3 ), 175 - 181 . https:// doi.org/10.1016/j.biopsych. 2011 . 12 .025.
Fontaine , R. G. , Yang , C. , Burks , V. S. , Dodge , K. A. , Price , J. M. , Pettit , G. S. , & Bates , J. E. ( 2009 ). Loneliness as a partial mediator of the relation between low social preference in childhood and anxious/depressed symptoms in adolescence . Development and Psychopathology , 21 ( 2 ), 479 - 491 . https://doi.org/10.1017/ S0954579409000261.
Gelernter , J. , Goldman , D. , & Risch , N. ( 1993 ). The A1 Allele at the D2 dopamine receptor gene and alcoholism: A reappraisal . JAMA , 269 ( 13 ), 1673 - 1677 . https://doi.org/10.1001/jama. 1993 . 03500130087038 .
Gillath , O. , Shaver , P. R. , Baek , J.-M. , & Chun , D. S. ( 2008 ). Genetic correlates of adult attachment style . Personality and Social Psychology Bulletin , 34 ( 10 ), 1396 - 1405 . https://doi.org/10.1177/ 0146167208321484.
Gimpl , G. , & Fahrenholz , F. ( 2001 ). The oxytocin receptor system: structure, function, and regulation . Physiological Reviews , 81 ( 2 ), 629 - 683 . https://doi.org/10.1152/physrev. 2001 . 81 .2.629.
Gong , P. , Fan , H. , Liu, J. , Yang , X. , Zhang , K. , & Zhou , X. ( 2017 ). Revisiting the impact of OXTR rs53576 on empathy: A population-based study and a meta-analysis . Psychoneuroendocrinology , 80 , 131 - 136 . https://doi.org/10.1016/j.psyneuen. 2017 . 03 .005.
Gooren , E. M. J. C. , Lier , P. A. C., van, Stegge, H. , Terwogt , M. M. , & Koot , H. M. ( 2011 ). The development of conduct problems and depressive symptoms in early elementary school children: The role of peer rejection . Journal of Clinical Child & Adolescent Psychology , 40 ( 2 ), 245 - 253 . https://doi.org/10.1080/15374416. 2011 . 546045 .
Gosso , M. F. , de Geus , E. J. C. , Polderman , T. J. C. , Boomsma , D. I. , Heutink , P. , & Posthuma , D. ( 2008 ). Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: Evidence of positive heterosis and gene-gene interaction on working memory functioning . European Journal of Human Genetics , 16 ( 9 ), 1075 - 1082 . https://doi.org/10.1038/ejhg. 2008 . 57 .
Hodges , E. V. , Boivin , M. , Vitaro , F. , & Bukowski , W. M. ( 1999 ). The power of friendship: Protection against an escalating cycle of peer victimization . Developmental Psychology , 35 ( 1 ), 94 - 101 .
Kiesner , J. ( 2002 ). Depressive symptoms in early adolescence: Their relations with classroom problem behavior and peer status . Journal of Research on Adolescence , 12 ( 4 ), 463 - 478 . https://doi. org/10.1111/ 1532 - 7795 . 00042 .
Kogan , A. , Saslow , L. R. , Impett , E. A. , Oveis , C. , Keltner , D. , & Saturn , S. R. ( 2011 ). Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition . Proceedings of the National Academy of Sciences , 108 ( 48 ), 19189 - 19192 . https://doi.org/10.1073/pnas.1112658108
Krueger , F. , Parasuraman , R. , Iyengar , V. , Thornburg , M. , Weel , J. , Lin , M. , et al. ( 2012 ). Oxytocin receptor genetic variation promotes human trust behavior. Frontiers in Human Neuroscience . https://doi.org/10.3389/fnhum. 2012 .00004
Kryski , K. R. , Smith , H. J. , Sheikh , H. I. , Singh , S. M. , & Hayden , E. P. ( 2014 ). Evidence for evocative gene-environment correlation between child oxytocin receptor (OXTR) genotype and caregiver behavior . Personality and Individual Differences , 64 , 107 - 110 . https://doi.org/10.1016/j.paid. 2014 . 02 .028.
Kusché , C. A. , & Greenberg , M. T. ( 1994 ). The PATHS curriculum . South Deerfield, MA: Channing-Bete Co .
Ladd , G. W. , & Troop-Gordon , W. ( 2003 ). The role of chronic peer difficulties in the development of children's psychological adjustment problems . Child Development , 74 ( 5 ), 1344 - 1367 . https://doi.org/10.1111/ 1467 - 8624 . 00611 .
Li , J. , Zhao , Y. , Li , R. , Broster , L. S. , Zhou , C. , & Yang , S. ( 2015 ). Association of oxytocin receptor gene (OXTR)rs53576 polymorphism with sociality: A meta-analysis . PLoS One , 10 ( 6 ), e0131820 https://doi.org/10.1371/journal.pone. 0131820 .
Lucht , M. J. , Barnow , S. , Sonnenfeld , C. , Rosenberger , A. , Grabe , H. J. , & Schroeder , W. , et al. ( 2009 ). Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects . Progress in NeuroPsychopharmacology and Biological Psychiatry , 33 ( 5 ), 860 - 866 . https://doi.org/10.1016/j.pnpbp. 2009 . 04 .004.
Lucht , M. J. , Barnow , S. , Sonnenfeld , C. , Ulrich , I. , Grabe , H. J. , & Schroeder , W. , et al. ( 2013 ). Associations between the oxytocin receptor gene (OXTR) and “mind-reading” in humans-An exploratory study . Nordic Journal of Psychiatry , 67 ( 1 ), 15 - 21 . https://doi.org/10.3109/08039488. 2012 . 700731 .
Luijk , M. P. C. M. , Roisman , G. I. , Haltigan , J. D. , Tiemeier , H. , Booth-LaForce , C. , & van IJzendoorn, M. H. , et al. ( 2011 ). Dopaminergic, serotonergic, and oxytonergic candidate genes associated with infant attachment security and disorganization? In search of main and interaction effects . Journal of Child Psychology and Psychiatry , 52 ( 12 ), 1295 - 1307 . https://doi.org/10. 1111/j.1469- 7610 . 2011 . 02440 .x.
McQuaid , R. J. , McInnis , O. A. , Matheson , K. , & Anisman , H. ( 2015 ). Distress of ostracism: Oxytocin receptor gene polymorphism confers sensitivity to social exclusion . Social Cognitive and Affective Neuroscience , 10 ( 8 ), 1153 - 1159 . https://doi.org/10. 1093/scan/nsu166.
Menting , B. , van Lier, P. A. C. , & Koot , H. M. ( 2011 ). Language skills, peer rejection, and the development of externalizing behavior from kindergarten to fourth grade . Journal of Child Psychology and Psychiatry , 52 ( 1 ), 72 - 79 . https://doi.org/10. 1111/j.1469- 7610 . 2010 . 02279 .x.
Middeldorp , C. M. , de Geus , E. J. C. , Beem , A. L. , Lakenberg , N. , Hottenga , J.-J., Slagboom , P. E. , & Boomsma , D. I. ( 2007 ). Family based association analyses between the serotonin transporter gene polymorphism (5-HTTLPR) and neuroticism, anxiety and depression . Behavior Genetics , 37 ( 2 ), 294 - 301 . https://doi. org/10.1007/s10519-006-9139-7.
Muthén , B. O. , & Khoo , S.-T. ( 1998 ). Longitudinal studies of achievement growth using latent variable modeling . Learning and Individual Differences , 10 ( 2 ), 73 - 101 . https://doi.org/10. 1016/S1041- 6080 ( 99 ) 80135 - 6 .
Muthén , L. K. , & Muthén , B. O. ( 1998 ). Mplus user's guide: Statistical analysis with latent variables . 7th ed. Los Angeles, CA: Muthén & Muthén . - 2015 .
Park , J. , Willmott , M. , Vetuz , G. , Toye , C. , Kirley , A. , & Hawi , Z. , et al. ( 2010 ). Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD . Progress in Neuro-Psychopharmacology and Biological Psychiatry , 34 ( 4 ), 697 - 702 . https://doi.org/10.1016/j.pnpbp. 2010 . 03 . 029.
Poulin , M. J. , Holman , E. A. , & Buffone , A. ( 2012 ). The neurogenetics of nice receptor genes for oxytocin and vasopressin interact with threat to predict prosocial behavior . Psychological Science , 23 ( 5 ), 446 - 452 . https://doi.org/10.1177/0956797611428471.
Rodrigues , S. M. , Saslow , L. R. , Garcia , N. , John , O. P. , & Keltner , D. ( 2009 ). Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans . Proceedings of the National Academy of Sciences of the United States of America , 106 ( 50 ), 21437 - 21441 . https://doi.org/10.1073/pnas.0909579106
Rose , A. J. , & Rudolph , K. D. ( 2006 ). A review of sex differences in peer relationship processes: Potential trade-offs for the emotional and behavioral development of girls and boys . Psychological Bulletin , 132 ( 1 ), 98 - 131 . https://doi.org/10.1037/ 0033 - 2909 . 132 . 1.98.
Satorra , A. ( 2000 ). Scaled and adjusted restricted tests in multi-sample analysis of moment structures . In Innovations in multivariate statistical analysis (pp. 233 - 247 ). Springer, Boston, MA. https:// doi.org/10.1007/978-1- 4615 -4603-0_ 17
Schwarz , G. ( 1978 ). Estimating the dimension of a model . The Annals of Statistics , 6 ( 2 ), 461 - 464 . https://doi.org/10.1214/aos/ 1176344136.
Sclove , S. L. ( 1987 ). Application of model-selection criteria to some problems in multivariate analysis . Psychometrika , 52 ( 3 ), 333 - 343 . https://doi.org/10.1007/BF02294360.
Skuse , D. H. , Lori , A. , Cubells , J. F. , Lee , I. , Conneely , K. N. , Puura , K. , et al. ( 2014 ). Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills . Proceedings of the National Academy of Sciences , 111 ( 5 ), 1987 - 1992 . https://doi.org/10.1073/pnas.1302985111
Slane , M. M. , Lusk , L. G. , Boomer , K. B. , Hare , A. E. , King , M. K. , & Evans , D. W. ( 2014 ). Social cognition, face processing, and oxytocin receptor single nucleotide polymorphisms in typically developing children . Developmental Cognitive Neuroscience , 9 , 160 - 171 . https://doi.org/10.1016/j.dcn. 2014 . 04 .001.
Statistics Netherlands . ( 2017 ). Statistics about population in the Netherlands from 2009 to 2016 . https://opendata.cbs.nl/statline/ #/CBS/en/dataset/37325eng/table?ts= 1523354633002
Tabak , B. A. , McCullough , M. E. , Carver , C. S. , Pedersen , E. J. , & Cuccaro , M. L. ( 2014 ). Variation in oxytocin receptor gene (OXTR) polymorphisms is associated with emotional and behavioral reactions to betrayal . Social Cognitive and Affective Neuroscience , 9 ( 6 ), 810 - 816 . https://doi.org/10.1093/scan/nst042.
Tops , M., van IJzendoorn , H, M. , Riem , M. M. E. , Boksem , M. A. S. , & Bakermans-Kranenburg , M. J. ( 2011 ). Oxytocin receptor gene associated with the efficiency of social auditory processing . Frontiers in Psychiatry. https://doi.org/10.3389/fpsyt. 2011 .00060
Van der Sar , A. M. , & Goudswaard , M. ( 2001 ). Docenthandleiding Taakspel voor Basisonderwijs . Rotterdam: Pedologisch Instituut.
van Lier , P. A. C. , & Koot , H. M. ( 2010 ). Developmental cascades of peer relations and symptoms of externalizing and internalizing problems from kindergarten to fourth-grade elementary school . Development and Psychopathology , 22 ( Special Issue 03 ), 569 - 582 . https://doi.org/10.1017/S0954579410000283.
van Roekel , E. , Verhagen , M. , Engels , R. C. M. E. , Goossens , L. , & Scholte , R. H. J. ( 2013 ). Oxytocin receptor gene (OXTR) in relation to loneliness in adolescence: interactions with sex, parental support, and DRD2 and 5-HTTLPR genotypes . Psychiatric Genetics , 23 ( 5 ), 204 - 213 . https://doi.org/10.1097/YPG. 0b013e328363f631.
van Roekel , E. , Verhagen , M. , Scholte , R. H. J. , Kleinjan , M. , Goossens , L. , & Engels , R. C. M. E. ( 2013 ). The oxytocin receptor gene (OXTR) in relation to state levels of loneliness in adolescence: Evidence for micro-level gene-environment interactions . PLoS One , 8 ( 11 ), e77689 https://doi.org/10.1371/journal. pone. 0077689 .
Verhagen , M. , Engels , R. , & Roekel , E. V. ( 2014 ). The oxytocin receptor gene (OXTR) and gazing behavior during social interaction: An observational study in young adults . Open Journal of Depression , 3 ( 4 ), 136 - 146 . https://doi.org/10.4236/ojd. 2014 . 34017 .
Waller , R. , Corral-Frías , N. S. , Vannucci , B. , Bogdan , R. , Knodt , A. R. , Hariri , A. R. , & Hyde , L. W. ( 2016 ). An oxytocin receptor polymorphism predicts amygdala reactivity and antisocial behavior in men . Social Cognitive and Affective Neuroscience , 11 ( 8 ), 1218 - 1226 . https://doi.org/10.1093/scan/nsw042.
Walum , H. , Lichtenstein , P. , Neiderhiser , J. M. , Reiss , D. , Ganiban , J. M. , & Spotts , E. L. , et al. ( 2012 ). Variation in the oxytocin receptor gene is associated with pair-bonding and social behavior . Biological Psychiatry , 71 ( 5 ), 419 - 426 . https://doi.org/10.1016/j. biopsych. 2011 . 09 .002.
Wang , J. , Qin , W. , Liu , B. , Zhou , Y. , Wang , D. , Zhang, Y. , Jiang , T. , & Yu , C. ( 2014 ). Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament . Brain Structure and Function , 219 ( 5 ), 1543 - 1554 . https://doi.org/10.1007/s00429- 013-0584-9.
Widaman , K. F. , & Thompson , J. S. ( 2003 ). On specifying the null model for incremental fit indices in structural equation modeling . Psychological Methods , 8 ( 1 ), 16 - 37 .
Williams , R. L. ( 2000 ). A note on robust variance estimation for cluster-correlated data . Biometrics , 56 ( 2 ), 645 - 646 . https://doi. org/10.1111/j. 0006 - 341X . 2000 . 00645 .x.
Wu , N. , & Su , Y. ( 2015 ). Oxytocin receptor gene relates to theory of mind and prosocial behavior in children . Journal of Cognition and Development , 16 ( 2 ), 302 - 313 . https://doi.org/10.1080/ 15248372. 2013 . 858042 .