C.E.M. van Beijsterveldt

The heritability of general cognitive ability increases linearly from childhood to young adulthood

Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite lifes ‘slings and arrows of outrageous fortune’, do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype–environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.

Genetics of the human electroencephalogram (EEG) and event-related brain potentials (ERPs): a review

Twin and family studies of normal variation in the human electroencephalogram (EEG) and event related potentials (ERPs) are reviewed. Most of these studies are characterized by small sample sizes. However, by summarizing these studies in one paper, we may be able to gain some insight into the genetic influences on individual differences in central nervous system functioning that may mediate genetically determined differences in behavior. It is clear that most EEG parameters are to a large extent genetically determined. The results for ERPs are based on a much smaller number of studies and suggest medium to large heritability.

Causes of Stability of Aggression from Early Childhood to Adolescence: A Longitudinal Genetic Analysis in Dutch Twins

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.

Heritability of Attention Problems in Children: I. Cross-Sectional Results From a Study of Twins, Age 3-12 Years

Multiple twin studies of attention problems (AP) from the Child Behavior Checklist or ADHD from the DSM criteria have reported on the genetic and environmental influences on these behaviors. The majority of these have studied AP and ADHD symptoms in twin samples combined across wide age spans, combined rater information and both genders. Thus, it is possible that the results are complicated by developmental, informant, and gender differences. The purpose of this study was to assess for the genetic and environmental contributions to overactive behavior (a syndrome highly related to AP in 7‐, 10‐, and 12‐years olds) in 3‐years olds (3,671 twin pairs), and attention problems in 7‐ (3,373 twin pairs), 10‐ (2,485 twin pairs), and 12‐years olds (1,305 twin pairs) while controlling for developmental, gender and rater contrast contributions. Using a cross‐sectional twin design, contributions from genetic additive, genetic dominance, unique environmental and rater contrast effects were estimated for CBCL maternal reports. We found that genetic influences on overactive behavior and attention problems are high across an age span that covers pre‐school and elementary school age. Although girls display less problem behavior compared to boys, heritability estimates were found equal for both genders at each age. Environmental experiences that are unique to the individual accounted for the remaining influence. At the age of 3 years, a rater contrast effect was detected. We hypothesize that the contrast effect represents a maternal rater bias effect that is dependent on the age of the twins. The implications of these findings are discussed with reference to the clinical setting and in the context of future research.

Individual Differences in Aggression: Genetic Analyses by age, gender, and informant in 3-, 7-, and 10-year-old Dutch Twins

Aggression in humans is associated with substantial morbidity and mortality. In this study we report on the aggressive behavior syndrome (AGG) in young children as defined by the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). We assessed aggression in a large sample of Dutch twins at ages 3, 7, and 10 years. The purpose of this study was three-fold. First, we determined the number of children who are “clinically deviant” on the AGG scale. Second, we assessed the genetic and environmental contributions to AGG for the maternal, paternal, and teacher ratings at each age, for boys and girls. Third, we explored issues of rater bias by analyzing parental and teacher data simultaneously. CBCL data were available from mothers on 6436 three-year-old, 5451 seven-year-old, and 2972 ten-year-old twin pairs and CBCL data from fathers on 4207 three-year-old, 4269 seven-year-old, and 2295 ten-year-old twin pairs. Teacher report data from the TRF were collected for 1036 seven-year-old and 903 ten-year-old twin pairs from the Netherlands Twin Registry. Structural equation modeling was employed to obtain genetic and environmental estimates at each age. Analyses were conducted separately by age and informant, as well as simultaneously, for all informants. Differences in raw scores across gender were found, with boys being rated as more aggressive than girls by all informants. Mothers reported more symptoms than fathers, who reported more symptoms than teachers. Evidence for moderate to high genetic influence (51%–72%) was seen for AGG by all three informants at all ages with only small sex differences in heritability estimates. Best fitting models for AGG by parent reports also included a small contribution of common environment. The largest sex differences in heritabilities were seen at age 10. Contributions of common (13%–27%) and unique (16%–31%) environment were small to moderate. There was some evidence of genetic dominance by teacher report for 10-year-old girls.

The Netherlands twin register biobank: A resource for genetic epidemiological studies

In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected. Fertile women were bled on day 2-4 of the menstrual cycle, or in their pill-free week. Biological samples were collected for DNA isolation, gene expression studies, creation of cell lines and for biomarker assessment. At the time of blood sampling, additional phenotypic information concerning health, medication use, body composition and smoking was collected. Of the participants contacted, 69% participated. Blood and urine samples were collected in 9,530 participants (63% female, average age 44.4 (SD 15.5) years) from 3,477 families. Lipid profile, glucose, insulin, HbA1c, haematology, CRP, fibrinogen, liver enzymes and creatinine have been assessed. Longitudinal survey data on health, personality and lifestyle are currently available for 90% of all participants. Genome-wide SNP data are available for 3,524 participants, with additional genotyping ongoing. The NTR biobank, combined with the extensive phenotypic information available within the NTR, provides a valuable resource for the study of genetic determinants of individual differences in mental and physical health. It offers opportunities for DNA-based and gene expression studies as well as for future metabolomic and proteomic projects.

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60–90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater‐independent and rater‐specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same‐sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater‐independent A/D were high in 3‐year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater‐specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater‐specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.

Genetic and Environmental Mechanisms Underlying Stability and Change in Problem Behaviors at Ages 3, 7, 10, and 12

Maternal ratings on internalizing (INT) and externalizing (EXT) behaviors were collected in a large, population-based longitudinal sample. The numbers of participating twin pairs at ages 3, 7, 10, and 12 were 5,602, 5,115, 2,956, and 1,481, respectively. Stability in both behaviors was accounted for by genetic and shared environmental influences. The genetic contribution to stability (INT: 43%; EXT: 60%) resulted from the fact that a subset of genes expressed at an earlier age was still active at the next time point. A common set of shared environmental factors operated at all ages (INT: 47%; EXT: 34%). The modest contribution of nonshared environmental factors (INT: 10%; EXT: 6%) could not be captured by a simple model. Significant age-specific influences were found for all components, indicating that genetic and environmental factors also contributed to changes in problem behavior.

Genetic contributions to long-range temporal correlations in ongoing oscillations

The amplitude fluctuations of ongoing oscillations in the electroencephalographic (EEG) signal of the human brain show autocorrelations that decay slowly and remain significant at time scales up to tens of seconds. We call these long-range temporal correlations (LRTC). Abnormal LRTC have been observed in several brain pathologies, but it has remained unknown whether genetic factors influence the temporal correlation structure of ongoing oscillations. We recorded the ongoing EEG during eyes-closed rest in 390 monozygotic and dizygotic twins and investigated the temporal structure of ongoing oscillations in the alpha- and beta-frequency bands using detrended fluctuation analysis (DFA). The strength of LRTC was more highly correlated in monozygotic than in dizygotic twins. Statistical analysis attributed up to ∼60% of the variance in DFA to genetic factors, indicating a high heritability for the temporal structure of amplitude fluctuations in EEG oscillations. Importantly, the DFA and EEG power were uncorrelated. LRTC in ongoing oscillations are robust, heritable, and independent of power, suggesting that LRTC and oscillation power are governed by distinct biophysical mechanisms and serve different functions in the brain. We propose that the DFA method is an important complement to classical spectral analysis in fundamental and clinical research on ongoing oscillations.

Genetic and environmental influences on EEG coherence

EEG coherence measures the covariation in electrical brain activity between two locations on the scalp and is used to study connectivity between cortical regions. The aim of this study was to determine the heritability of EEG coherence. Coherence was measured in a group of 213 16-yr-old twin pairs. By including male and female twin pairs in the sample, sex differences in genetic architecture were systematically examined. The EEG was obtained during quiet supine resting. Coherence was estimated for short and long distance combinations of electrode pairs along the anterior-posterior axis within a hemisphere for four frequency bands (delta, theta, alpha and beta). Averaged over all electrode combinations about 60% of the variance was explained by genetic factors for coherence in the theta, alpha and beta bands. For the delta band, the heritability was somewhat lower. No systematic sex differences in genetic architecture were found. All environmental influences were nonshared, i.e., unique factors including measurement error. Environmental factors shared by twin siblings did not influence variation in EEG coherence. These results suggest that individual differences in coherence form a potential candidate for (molecular) genetic studies on brain function.