G.C.M. van Baal

Genetic and environmental influences on the development of intelligence

Measures of intelligence were collected in 209 twin pairs at 5, 7, 10, and 12 years of age, as part of a longitudinal project on intelligence, brain function, and behavioral problems. Intelligence was measured at 5, 7, and 10 years of age with the RAKIT, a well-known Dutch intelligence test, consisting of 6 subscales. At 12 years of age, the complete WISC-R was administered (12 subscales). Both intelligence tests resulted in a measure of full-scale IQ (FSIQ). Participation rate is around 93% at age 12. Correlation coefficients over time are high: (r(5–7) = .65; r(5–10) = .65; r(5–12) = .64; r(7–10) = .72; r(7–12) = .69 and r(10–12) = .78). Genetic analyses show significant heritabilities at all ages, with the expected increase of genetic influences and decrease of shared environmental influences over the years. Genetic influences seem to be the main driving force behind continuity in general cognitive ability, represented by a common factor influencing FSIQ at all ages. Shared environmental influences are responsible for stability as well as change in the development of cognitive abilities, represented by a common factor influencing FSIQ at all ages and age-specific influences, respectively.

The genetics of coronary heart disease: The contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Brain Plasticity and Intellectual Ability Are Influenced by Shared Genes

Although the adult brain is considered to be fully developed and stable until senescence when its size steadily decreases, such stability seems at odds with continued human (intellectual) development throughout life. Moreover, although variation in human brain size is highly heritable, we do not know the extent to which genes contribute to individual differences in brain plasticity. In this longitudinal magnetic resonance imaging study in twins, we report considerable thinning of the frontal cortex and thickening of the medial temporal cortex with increasing age and find this change to be heritable and partly related to cognitive ability. Specifically, adults with higher intelligence show attenuated cortical thinning and more pronounced cortical thickening over time than do subjects with average or below average IQ. Genes influencing variability in both intelligence and brain plasticity partly drive these associations. Thus, not only does the brain continue to change well into adulthood, these changes are functionally relevant because they are related to intelligence.

Genetic influences on thinning of the cerebral cortex during development

During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Brocas area), and left parietal (Wernickes area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.

Genetic architecture of EEG power spectra in early life

We measured the electroencephalogram (EEG) in 209 5 year old monozygotic (MZ) and dizygotic (DZ) twin pairs to estimate the relative contribution of genetic and environmental factors to EEG power spectra in early life. Data from same-sex and from opposite-sex twin pairs were used to test for sex differences in genetic influences. Results showed high concordance for EEGs of MZ twins for absolute and relative power in delta, theta, alpha 1, alpha 2, beta 1 and beta 2 bands. A model with additive genetic and unique environmental influences explained individual differences in both absolute and relative power in almost all bands and all electrode positions. Heritability of EEG power spectra was high. For absolute power the highest heritabilities were observed in theta, alpha 1, alpha 2 and beta 1 power bands (mean heritability 81, 81, 78, and 73%, respectively). Somewhat lower heritabilities were found in delta and beta 2 bands (mean heritability 55 and 64%, respectively). For relative power heritabilities were 63, 76, 71, 72, 68, and 65 for delta, theta, alpha 1, alpha 2, beta 1, and beta 2, respectively. Virtually no sex differences in heritability were found. These findings indicate that the background EEG is one of the most heritable characteristics in early life.

The Dutch Twin Register: Growth data on Weight and Height

As part of a longitudinal developmental study of newborn and young Dutch twins, data on weight and height are collected. Birth weight and height are available for 3275 pairs; data on growth, for 1390 pairs.

Stability of genetic and environmental influences on P300 amplitude: a longitudinal study in adolescent twins.

This study examined the stability of genetic and environmental influences on individual differences in P300 amplitude during adolescence. The P300 component is an event-related brain potential (ERP) that has attracted much attention as a biological marker for disturbed cognitive processing in psychopathology. Understanding the genetics of this biological marker may contribute to understanding the genetics of the associated psychopathologies. In a group of 213 adolescent twin pairs, the P300 component was measured twice, the first time at age 16 and the second time 18 months later. A large part of the variance of the P300 amplitude could be explained by familial factors, with estimates ranging from 30% to 81%. Whether the familial resemblance was due to genetic or shared environmental factors depended on sex. For males, genetic factors explained familial resemblance in P300 amplitude, but for females such resemblance was likely due to shared environmental factors. The phenotypic stability of the P300 amplitude from 16 to 18 years was high in both sexes, and stability could be attributed largely to the same familial factors. There was no evidence that new familial influences emerged at age 18.

Genetic Correlation Between the P300 Event-Related Brain Potential and the EEG Power Spectrum

Previous studies have demonstrated moderate heritability of the P300 component of event-related brain potentials (ERPs) and high heritability of background electroencephalogram (EEG) power spectrum. However, it is unclear whether EEG and ERPs are influenced by common or independent genetic factors. This study examined phenotypic and genetic correlations between EEG spectral power and P300 amplitude using data from 206 Dutch twin pairs, age 16 years. Multivariate genetic models (Cholesky decomposition) were fitted to the observed twin covariances using Mx software. In males, genetic correlations between P300 and EEG power measures were high (0.54–0.74); 30% of the total P300 variance could be explained by genetic factors influencing EEG delta power and 26% by P300-specific genetic factors (total heritability 56%). In females, 45% of P300 variance could be attributed to familial influences that were shared with the EEG. However, it was not possible to distinguish between the genetic versus shared environmental factors, consistent with previous analysis of P300 in this sample (van Beijsterveldt et al., 1998). The results suggest that a substantial proportion of genetic influences on P300 amplitude can be explained by strong heritability of slow EEG rhythms contributing to P300.

Scale-Free Modulation of Resting-State Neuronal Oscillations Reflects Prolonged Brain Maturation in Humans

Human neuronal circuits undergo life-long functional reorganization with profound effects on cognition and behavior. Well documented prolonged development of anatomical brain structures includes white and gray matter changes that continue into the third decade of life. We investigated resting-state EEG oscillations in 1433 subjects from 5 to 71 years. Neuronal oscillations exhibit scale-free amplitude modulation as reflected in power-law decay of autocorrelations—also known as long-range temporal correlations (LRTC)—which was assessed by detrended fluctuation analysis. We observed pronounced increases in LRTC from childhood to adolescence, during adolescence, and even into early adulthood (∼25 years of age) after which the temporal structure stabilized. A principal component analysis of the spatial distribution of LRTC revealed increasingly uniform scores across the scalp. Together, these findings indicate that the scale-free modulation of resting-state oscillations reflects brain maturation, and suggests that scaling analysis may prove useful as a biomarker of pathophysiology in neurodevelopmental disorders such as attention deficit hyperactivity disorder and schizophrenia.

Longitudinal genetic analysis of EEG coherence in young twins

During middle childhood, continuous changes occur in electroencephalogram (EEG) coherence, an index of cortico-cortical connectivity of the brain. In the gradual development of EEG coherence, occasional “growth spurts” are observed which coincide with periods of discontinuous development in cognition. Discontinuous development may reflect changes in the genetic architecture of a trait over time, for instance, by the emergence of new genetic factors. To examine stability and change in genetic and environmental influences on EEG coherence from ages 5 to 7 years, intrahemispheric EEG coherences from 14 connections were collected twice in 209 twin pairs. Overall, heritabilities (h2) were moderate to high for all EEG coherences at both ages (average: 58%). For occipito-cortical connections in the right hemisphere, h2 increased with age due to a decrease in environmental variance. For prefronto-cortical connections in the left hemisphere, h2 decreased with age due to a decrease in genetic variance. New genetic factors at age 7 were found for prefronto-parietal coherence, and centro-occipital and parieto-occipital EEG coherences in both hemispheres and, in the left hemisphere, for prefronto-frontal EEG coherences. Mean genetic correlation for these cortico-cortical connections over time was 0.72, indicating that at least part of the genetic influences is age-specific. We argue that this is convincing evidence for the existence of stage-wise brain maturation from years 5 to 7, and that growth spurts in EEG coherence may be part of the biological basis for discontinuous cognitive development at that age range.