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Neuroticism has societal, mental and physical health relevance, with an etiology involving genetic predisposition, psychological influence, and their interaction.
To understand whether the association between polygenic risk score for neuroticism (PRS-N) and neuroticism is moderated by affective well-being.
Data were derived from TwinssCan, a general population twin cohort (age range=15-35 years, 478 monozygotic twins). Self-report questionnaires were used to measure well-being and neuroticism. PRS-N was trained from the Genetics of Personality Consortium (GPC) and United Kingdom Biobank (UKB). Multilevel mixed-effects models were used to test baseline and changes in well-being and neuroticism.
Baseline wellbeing and neuroticism were associated (β=-1.35, p<0.001). PRSs-N were associated with baseline neuroticism (lowest p-value: 0.008 in GPC, 0.01 in UKB). In interaction models (PRS x wellbeing), GPC PRS-N (β=0.38, p=0.04) and UKB PRS-N (β=0.81, p<0.001) had significant interactions.
PRSs-N were associated with changes in neuroticism (lowest p-value: 0.03 in GPC, 0.3 in UKB). Furthermore, changes in wellbeing and neuroticism were associated (β =-0.66, p<0.001). In interaction models (PRS x change in wellbeing), only UKB PRS-N had a significant interaction (β=0.80, p<0.001).
Interaction between polygenic risk, wellbeing and neuroticism, were observed regarding baselines measures and change over time. Depending on the analysis step, the direction of the effect changed.
Prior evidence suggests that men and women might be differentially susceptible to distinct types of childhood adversity (CA), but research on gender-specific associations between CA subtypes and psychiatric symptoms is limited.
To test the gender-specific associations of CA subtypes and psychiatric symptoms in the general population.
Data from 791 twins and siblings from the TwinssCan project were used. Psychopathology and CA exposure were assessed using the Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire (CTQ), respectively. The associations between the total CTQ scores and SCL-90 scores (i.e. total SCL-90, psychoticism, paranoid ideation, anxiety, depression, somatization, obsessive-compulsive, interpersonal sensitivity, hostility, and phobic anxiety) were tested in men and women separately. The associations between the five CA subtypes (i.e. physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect) and total SCL-90 were tested in a mutually adjusted model. As exploratory analyses, the associations between all CA subtypes and the nine SCL-90 subdomain scores were similarly tested. The regression coefficients between men and women were compared using Chow’s test. All models were adjusted for age and family structure.
Total CTQ was significantly associated with total SCL-90 in men (B = 0.013, SE = 0.003, P < .001) and women (B = 0.011, SE = 0.002, P < .001). The associations with the nine symptom domains were also significant in both genders (P < .001). No significant gender differences in the regression coefficients of total CTQ were detected. The analyses of CA subtypes showed a significant association between emotional abuse and total SCL-90 in women (B = 0.173, SE = 0.030, P < .001) and men (B = 0.080, SE = 0.035, P = .023), but the association was significantly stronger in women (ꭓ2(1) = 4.10, P = .043). The association of sexual abuse and total SCL-90 was only significant in women (B = 0.217, SE = 0.053, P < .001). The associations of emotional neglect (B = 0.061, SE = 0.027, P = .026) and physical neglect (B = 0.167, SE = 0.043, P < .001) with total SCL-90 were only significant in men. The explorative analyses of SCL-90 subdomains revealed significant associations of emotional abuse with all nine symptom domains and of sexual abuse with seven symptom domains in women. Significant associations of physical neglect with six symptom domains and of emotional neglect with depression were also detected in men. No other significant associations between CT subtypes and total SCL-90 or symptom domain scores were observed in men and women.
CA exposure was associated with diverse psychopathology similarly in both genders. However, women are more sensitive to abuse, but men are more sensitive to neglect. Gender-specific influences of CA subtypes on psychopathology should be considered in future studies.
The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology.
We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15–34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model.
Linear analyses showed that emotional stress reactivity was not associated with onset (ß = .02; P = .56) or persistence (ß = -.01; P = .78) of symptoms. There was a significant effect of baseline symptom score (ß = .53; P < .001) and average negative affect (NA: ß = .19; P < .001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (ß = .25; P < .001), but not moderate (ß = -.03; P = .65) or severe (ß = -.06; P = .42), stressors was associated with symptom persistence one year later.
We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
In liquid spray applications, the sprays are often created by the formation and destabilization of a liquid sheet or jet. The disadvantage of such atomization processes is that the breakup is often highly irregular, causing a broad distribution of droplet sizes. As these sizes are controlled by the ligament corrugation and size, a monodisperse spray should consist of ligaments that are both smooth and of equal size. A straightforward way of creating smooth and equally sized ligaments is by droplet impact on a mesh. In this work we show that this approach does however not produce monodisperse droplets, but instead the droplet size distribution is very broad, with a large number of small satellite drops. We demonstrate that the fragmentation is controlled by a jet instability, where initial perturbations caused by the injection process result in long-wavelength disturbances that determine the final ligament breakup. During destabilization the crests of these disturbances are connected by thin ligaments which are the leading cause of the large number of small droplets. A secondary coalescence process, due to small relative velocities between droplets, partly masks this effect by reducing the amount of small droplets. Of the many parameters in this system, we describe the effect of varying the mesh size, mesh rigidity, impact velocity and wetting properties, keeping the liquid properties the same by focusing on water droplets only. We further perform lattice Boltzmann modelling of the impact process that reproduces key features seen in the experimental data.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Intrauterine factors important for cognitive development, such as birth weight, chorionicity and umbilical cord characteristics were investigated. A total of 663 twin pairs completed the Wechsler Intelligence Scale for Children-Revised and scores were available for Performance, Verbal and Total Intelligence Quotient (IQ). The intrauterine factors examined were birth weight, placental weight and morphology, cord knots, cord length and cord insertion. IQ scores for the varying levels of the intrauterine markers adjusting for gender and gestational age were calculated. The heritability of IQ and the association between IQ and intrauterine environment were examined. Twins with lower birth weight and cord knots had lower IQ scores. The aetiology of IQ is largely distinct from that of birth weight and cord knots, and non-shared environment may influence the observed relationships.
The assessment of fetal growth is an essential component of good antenatal care, especially for twins. The aims of this study are to develop twin-specific intrauterine 'growth' charts, based on cross-sectional birthweight data, for monochorionic and dichorionic twins according to sex and parity, and to detect twins at risk for neonatal death by comparing the use of twin-specific and singleton charts. The study sample consisted of 76,471 singletons and 8454 twins (4227 pairs) born in East Flanders (Belgium). Birthweights were analyzed using a nonlinear Gaussian regression. After 33 weeks of gestation, the birthweights of twins started to deviate from singletons (difference of 900 grams at 42 weeks). Birthweights of dichorionic twins continued to increase, whereas those of monochorionic twins decreased after week 40 (difference of more than 300 g at 42 weeks). After 31 weeks of gestation, neonatal mortality increased as centile decreased, and was especially high if birthweight was below the twin-specific third centile: .032 (below) versus .007 (above). Using singleton centiles, this was less obvious. In conclusion, twin-specific growth charts, taking chorionicity into account, are more accurate to detect twins at risk for neonatal death. Therefore the presented charts, based on cross-sectional birthweight data, enable an improved assessment of twin growth.
Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARγ and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.
Negative life events are strongly associated with the development of depression. However, the etiologic relationship between life events and depression is complex. Evidence suggests that life events can cause depression, and depression increases the risk for life events. Additionally, third factors influencing both phenotypes may be involved. In this work we sought to disentangle these relationships using a genetically informative longitudinal design.
Adult female twins (n=536, including 281 twin pairs) were followed up for measurements of negative life event exposure and depressive symptoms. Four follow-ups were completed, each approximately 3 months apart. Model fitting was carried out using the Mx program.
The best-fitting model included causal paths from life events to depressive symptoms for genetic and shared environmental risk factors, whereas paths from depressive symptoms to life events were apparent for shared environmental factors. Shared latent influence on both phenotypes was found for individual-specific effects.
Life events and depressive symptoms have complex inter-relationships that differ across sources of variance. The results of the model, if replicated, indicate that reducing life event exposure would reduce depressive symptoms and that lowering depressive symptoms would decrease the occurrence of negative life events.
Genes for depression may act by making individuals more sensitive to childhood trauma. Given that childhood adversity is a risk factor for adult psychosis and symptoms of depression and psychosis tend to cluster within individuals and families, the aim was to examine whether the association between childhood adversity and psychotic-like symptoms is moderated by genetic liability for depression. A secondary aim was to determine to what degree a depression-related increase in stress sensitivity or depressive symptoms themselves occasioned the moderating effect.
Female twins (n=508) completed both prospective and retrospective questionnaires regarding childhood adversity [the Symptom Checklist-90 – Revised (SCL-90-R) and SCID-I (psychotic symptoms)] and psychotic trait liability [the Community Assessment of Psychic Experiences (CAPE)]. Stress sensitivity was indexed by appraisals of event-related stress and negative affect (NA) in the flow of daily life, assessed with momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of childhood adversity by genetic liability for depression in the prediction of follow-up psychotic experiences.
The effect of childhood adversity was significantly moderated by genetic vulnerability for depression in the model of both follow-up psychotic experiences (SCL-90-R) and follow-up psychotic trait liability (CAPE). The moderation by genetic liability was mediated by depressive experience but not by stress sensitivity.
Genetic liability for depression may potentiate the pathway from childhood adversity to psychotic-like symptoms through dysfunctional emotional processing of anomalous experiences associated with childhood trauma.
Traumatic life events are generally more common in patients with borderline personality disorder (BPD) than in non-patients or patients with other personality disorders. This study investigates whether exposure to life events moderates the genetic architecture of BPD features. As the presence of genotype–environment correlation (rGE) can lead to spurious findings of genotype–environment interaction (G×E), we also test whether BPD features increase the likelihood of exposure to life events.
The extent to which an individual is at risk to develop BPD was assessed with the Personality Assessment Inventory – Borderline features scale (PAI-BOR). Life events under study were a divorce/break-up, traffic accident, violent assault, sexual assault, robbery and job loss. Data were available for 5083 twins and 1285 non-twin siblings. Gene–environment interaction and correlation were assessed by using structural equation modelling (SEM) and the co-twin control design.
There was evidence for both gene–environment interaction and correlation. Additive genetic influences on BPD features interacted with the exposure to sexual assault, with genetic variance being lower in exposed individuals. In individuals who had experienced a divorce/break-up, violent assault, sexual assault or job loss, environmental variance for BPD features was higher, leading to a lower heritability of BPD features in exposed individuals. Gene–environment correlation was present for some life events. The genes that influence BPD features thus also increased the likelihood of being exposed to certain life events.
To our knowledge, this study is the first to test the joint effect of genetic and environmental influences and the exposure to life events on BPD features in the general population. Our results indicate the importance of both genetic vulnerability and life events.
Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity.
Twin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA.
All three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity.
The findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.
Most of our knowledge about borderline personality disorder features has been obtained through the study of clinical samples. Although these studies are important in their own right, they are limited in their ability to address certain important epidemiological and aetiological questions such as the degree to which there is a genetic influence on the manifestation of borderline personality disorder features. Though family history studies of borderline personality disorder indicate genetic influences, there have been very few twin studies and the degree of genetic influence on borderline personality disorder remains unclear.
Data were drawn from twin samples from The Netherlands (n=3918), Belgium (n=904) and Australia (n=674). In total, data were available on 5496 twins between the ages of 18 and 86 years from 3644 families who participated in the study by completion of a mailed self-report questionnaire on borderline personality disorder features.
In all countries, females scored higher than males and there was a general tendency for younger adults to endorse more borderline personality disorder features than older adults. Model-fitting results showed that additive genetic influences explain 42% of the variation in borderline personality disorder features in both men and women and that this heritability estimate is similar across The Netherlands, Belgium and Australia. Unique environmental influences explain the remaining 58% of the variance.
Genetic factors play a role in individual differences in borderline personality disorder features in Western society.
Background. Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene–environment interaction in a twin design.
Method. The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6–17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs.
Results. A main independent effect of lower birth weight, corrected for gestational age (small for gestational age – SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour.
Conclusions. Results are suggestive of negative gene–birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.
Most population studies of twins estimate the number of monozygotic (MZ) and dizygotic (DZ) pairs by Weinberg's differential rule. This rule assumes that within the DZ twins the numbers of unlike-sexed (U) and like-sexed (L) twins are equal. The literature on the validity of Weinberg's rule is still controversial. In this prospective population-based study (EFPTS) of 2,589 twin pairs, of whom 2,577 were of known zygosity and placentation, the estimates of Weinberg's rule agree well with the results of direct zygosity determination.
The more that twin and other multiple pregnancies are investigated, the more it becomes mandatory that collaborative studies are set up in order to attain the criticai number of cases needed to achieve meaningful and reliable results. The European Multiple Birth Study (EMBS) aims to study two aspects of twin and multiple pregnancy: 1) management of pregnancy and labour, with emphasis on the prevention of preterm delivery; 2) accurate determination of zygosity, a prerequisite for the proper use of the twin method in a variety of fields, eg, congenital malformations, genetics, clinical investigations, etc. The rationale, the methods and the organisation of the study are described and discussed.
Classical psychological twin studies have yielded in part equivocal and sometimes contradictory results. Besides the complexity of the problem, the delicate character of the diagnosis, and the rudimentary tools which were used, several other factors are underlying this situation: (1) insufficient systematization of the set-up and the careless design of the investigations; (2) lack of follow-up studies; (3) uncertain diagnosis of zygosity; in MZ twins no attention to the age of the ovum at the time of cleavage; (4) lack of consideration for antenatal and perinatal influences; (5) no attention to the typical circumstances linked to the twin situation. All this makes it difficult to balance nature against nurture on the basis of comparison between MZ twins, DZ twins, and singletons. Interactions may also appear between the effect of twinning and other factors such as the socioeconomic circumstances. A new investigation was therefore started where, besides the twins, a group of matched control singletons was constituted. The follow-up study is now completed up to the age of 5 years in 13 MZ and 20 DZ twin pairs (+ controls, that is to say, 99 children).
The children were observed and subjected to psychological tests at the age of 6 months and of 1, 2, 3, 4, and 5 years.