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AbstractTwin studies that examine the effect of specific environmental risk factors on psychiatric disorders assume that there are no differences in prevalences of these risk factors between twins and singletons. Violation of this assumption signifies that the results from twin studies might not generalize to singletons. Another assumption, not only often underlying twin studies but also epidemiological research, is that life- events are not influenced by familial factors. We tested differences in prevalences of experienced life events in a Dutch sample of 2086 monozygotic (MZ) twins, 2090 dizygotic (DZ) twins and 1307 of their siblings. Self-reported data on life events (illness of self, illness of a significant other, spouse/romantic relationship, divorce/break-up of a relationship, death of a significant other, traffic accident, robbery, violent assault, sexual assault) were available from a survey- study. We further investigated whether familial resemblance was present for the exposure to these life events and, if so, whether this resemblance was due to genetic or common environmental factors. No differences were found in the prevalences of life events between MZ twins, DZ twins and their siblings. There was evidence for familial aggregation of all life events, except for traffic accidents in women. Results indicated genetic control on the presence of a spouse or involvement in a relationship. Familial resemblance of illness and death of a significant other was mainly due to common environment. For the other life events, it was not possible to distinguish between genetic and common environmental effects.

AbstractThe hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.

Neuroimaging studies have indicated abnormalities in cortico-striato-thalamo-cortical circuits in obsessive–compulsive disorder patients, but results have not been consistent. Since there are significant sex differences in human brain anatomy and obsessive–compulsive symptomatology and its developmental trajectories tend to be distinct in males and females, we investigated whether sex is a potential source of heterogeneity in neuroimaging studies on obsessive–compulsive symptoms. We selected male and female twin pairs who were concordant for scoring either high or low for obsessive–compulsive symptoms and a group of discordant pairs where one twin scored high and the co-twin scored low. The design included 24 opposite-sex twin pairs. Magnetic resonance imaging scans of 31 males scoring high for obsessive–compulsive symptoms, 41 low-scoring males, 58 high-scoring females, and 73 low-scoring females were analyzed and the interaction of obsessive–compulsive symptoms by sex on gray matter volume was assessed using voxel-based morphometry. An obsessive–compulsive symptom by sex interaction was observed for the left middle temporal gyrus, the right middle temporal gyrus, and the right precuneus. These interactions acted to reduce or hide a main effect in our study and illustrate the importance of taking sex into account when investigating the neurobiology of obsessive–compulsive symptoms.

A new genetic factor model for multivariate phenotypic time series, iFACE, is presented which allows for the estimation of subject-specific model parameters of genetic and environmental factors. The iFACE was applied to multivariate EEG registrations obtained with single dizygotic twin pairs. The results showed evidence for considerable subject-specificity in heritabilities and environmental effects. The assumption that the population is homogeneous (i.e., that each case in the population obeys the same parametric model), does not hold for these psychophysiological data, and its use should be critically reconsidered. We conclude that the iFACE provides a powerful new methodology to assess heterogeneity (subject-specificity) based on phenotypic observations.

This article concerns the power of various data analytic strategies to detect the effect of a single genetic variant (GV) in multivariate data. We simulated exactly fitting monozygotic and dizygotic phenotypic data according to single and two common factor models, and simplex models. We calculated the power to detect the GV in twin 1 data in an ANOVA of phenotypic sum scores, in a MANOVA, and in exploratory factor analysis (EFA), in which the common factors are regressed on the genetic variant. We also report power in the full twin model, and power of the single phenotype ANOVA. The results indicate that (1) if the GV affects all phenotypes, the sum score ANOVA and the EFA are most powerful, while the MANOVA is less powerful. Increasing phenotypic correlations further decreases the power of the MANOVA; and (2) if the GV affects only a subset of the phenotypes, the EFA or the MANOVA are most powerful, while sum score ANOVA is less powerful. In this case, an increase in phenotypic correlations may enhance the power of MANOVA and EFA. If the effect of the GV is modeled directly on the phenotypes in the EFA, the power of the EFA is approximately equal to the power of the MANOVA.

AbstractWe investigated whether women show larger heart rate variability (HRV) than men after controlling for a large number of health-related covariates, using two indices of HRV, namely respiratory sinus arrhythmia (RSA) and approximate entropy (ApEn). In a twin design, the heritability of both indices was examined. The covariation between RSA and ApEn, a measure of heart rate dynamics derived from nonlinear dynamical systems theory, was decomposed into genetic and environmental components. Subjects were 196 male and 210 female middle-aged twins. Females showed larger HRV than men before (ApEn: p < .001; RSA: p = .052) and after adjustment for covariates (ApEn: p < .001; RSA: p = .015). This sex difference was confirmed by significant intrapair differences in the opposite-sex twin pairs for both ApEn (p < .001) and RSA (p = .03). In addition to sex, only heart period and age (both p < .001) were found to be independent predictors of ApEn, whereas RSA was also influenced by respiration rate and smoking (both p < .001). Age explained 16% and 6% of the variance in RSA and ApEn, respectively. Oral contraceptive use and menopausal status had no effect on HRV. Genetic model fitting yielded moderate heritability estimates for RSA (30%) and ApEn (40%) for both males and females. The correlation between RSA and ApEn (r = .60) could be attributed to genetic factors (48%), environmental factors (36%) and age (16%). The present study found support for a gender difference in HRV with women having greater HRV than men even after controlling for a large number of potential confounders. Indices of heart rate dynamics derived from nonlinear dynamical systems theory are moderately heritable and may be more sensitive than traditional indices of HRV to reveal subtle sex differences with important implications for health and disease.

Migraine and tension-type headache (TTH) are often viewed as distinct entities and defined as such in the International Classification of Headache Disorders, 2nd edition (ICHD-II) criteria, although there is also empirical evidence to suggest they may be etiologically similar. This study aims to investigate whether migraine and TTH are etiologically related conditions. First, we explored whether migraine and TTH were associated with the same environmental and lifestyle risk factors at the population level. Second, we examined comorbidity of migraine and TTH in a twin design. By comparing the associations in monozygotic (MZ) and dizygotic (DZ) twin pairs, we investigated whether the comorbidity can be explained by genetic factors that influence both conditions. Results indicated that migraine and TTH were largely associated with the same environmental and lifestyle factors, including younger age, female sex, higher body mass index, more depression, stress at home, and less participation in regular exercise, with consistently stronger effects for migraine than for TTH. Migraine in one twin was significantly associated with TTH in the other twin. A stronger cross-trait, cross-twin association in MZ than DZ twins suggested that this comorbidity may also be partly due to shared genetic factors, although the difference in associations was not significant. In conclusion, our findings are consistent with the hypothesis that migraine and TTH have partly shared etiologies. For both treatment and research, it may be advisable not to make a rigid distinction, but to treat migraine and TTH as related conditions.

Twin research has offered evidence that monozygotic (MZ) twins are more socially close than dizygotic (DZ) twins, but has not paid much attention to the way twins compare themselves with their co-twin. The few studies in this area suggest that 'horizontal comparisons' (social comparison motivated by solidarity or communion with others) matter more for MZ twins than for DZ twins, at least when the co-twin is the social comparison standard. Consistent with this view, we predicted higher interest in MZ twins relative to DZ twins to select their co-twin rather than other people in general as the social comparison standard. The Social Comparison Orientation (SCO) scale, which measures the inclination to compare with others in a horizontal rather than vertical mode (comparing either upward or downward), was administered in 90 MZ pairs and 57 same-sex DZ pairs (63% female; average age 18.06 years) from the Netherlands Twin Register. MZ twin pairs showed significantly higher SCO scores than DZ twin pairs (with a large effect size) on the co-twin SCO, whereas the two groups did not differ from each other on the general SCO excluding the co-twin as social comparison standard. In MZ twin pairs, anxiety was associated with social comparison with others in general, not with their co-twin. For both scales, twin resemblance was explained by additive genetic variance. The present findings provide direct evidence that horizontal comparisons with the co-twin are of particular importance for MZ twins.

In order to estimate the influence of genetic and environmental factors on 'crying without a cause' and 'being easily upset' in 2-year-old children, a large twin study was carried out. Prospective data were available for ~18,000 2-year-old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis was performed using structural equation modeling in the Mx software package. The influence of maternal personality characteristics and demographic and lifestyle factors was tested to identify specific risk factors that may underlie the shared environment of twins. Furthermore, it was tested whether crying without a cause and being easily upset were predictive of later internalizing, externalizing and attention problems. Crying without a cause yielded a heritability estimate of 60% in boys and girls. For easily upset, the heritability was estimated at 43% in boys and 31% in girls. The variance explained by shared environment varied between 35% and 63%. The correlation between crying without a cause and easily upset (r = .36) was explained both by genetic and shared environmental factors. Birth cohort, gestational age, socioeconomic status, parental age, parental smoking behavior and alcohol use during pregnancy did not explain the shared environmental component. Neuroticism of the mother explained a small proportion of the additive genetic, but not of the shared environmental effects for easily upset. Crying without a cause and being easily upset at age 2 were predictive of internalizing, externalizing and attention problems at age 7, with effect sizes of .28–.42. A large influence of shared environmental factors on crying without a cause and easily upset was detected. Although these effects could be specific to these items, we could not explain them by personality characteristics of the mother or by demographic and lifestyle factors, and we recognize that these effects may reflect other maternal characteristics. A substantial influence of genetic factors was found for the two items, which are predictive of later behavioral problems.