Three-and-a-half-factor model? The genetic and environmental structure of the CBCL/6-18 internalizing grouping.

In the present article, multivariate genetic item analyses were employed to address questions regarding the ontology and the genetic and environmental etiology of the Anxious/Depressed, Withdrawn, and Somatic Complaints syndrome dimensions of the Internalizing grouping of the Child Behavior Checklist/6-18 (CBCL/6-18). Using common and independent pathway genetic factor modeling, it was examined whether these syndrome dimensions can be ascribed a realist ontology. Subsequently, the structures of the genetic and environmental influences giving rise to the observed symptom covariation were examined. Maternal ratings of a population-based sample of 17,511 Dutch twins of mean age 7.4 (SD = 0.4) on the items of the Internalizing grouping of the Dutch CBCL/6-18 were analyzed. Applications of common and independent pathway modeling demonstrated that the Internalizing syndrome dimensions may be better understood as a composite of unconstrained genetic and environmental influences than as causally relevant entities generating the observed symptom covariation. Furthermore, the results indicate a common genetic basis for anxiety, depression, and withdrawn behavior, with the distinction between these syndromes being driven by the individual-specific environment. Implications for the substantive interpretation of these syndrome dimensions are discussed.

Genetic and environmental stability of intelligence in childhood and adolescence.

The present study examined the genetic and environmental contributions to the temporal stability of verbal, non-verbal and general intelligence across a developmental period spanning childhood and adolescence (5-18 years). Longitudinal twin data collected in four different studies on a total of 1,748 twins, comprising 4,641 measurement points in total, were analyzed using genetic adaptations of the simplex model. The heterogeneity in the type of instrument used to assess psychometric intelligence across the different subsamples and ages allowed us to address the auxiliary question of how to optimally utilize the existing longitudinal data in the context of gene-finding studies. The results were consistent across domains (verbal, non-verbal and general intelligence), and indicated that phenotypic stability was driven primarily by the high stability of additive genetic factors, that the stability of common environment was moderate, and that the unique environment contributed primarily to change. The cross-subscale stability was consistently low, indicating a small overlap between different domains of intelligence over time. The high stability of additive genetic factors justifies the use of a linear combination of scores across the different ages in the context of gene-finding studies.

Genetic variation at the TPH2 gene influences impulsivity in addition to eating disorders.

Genes are involved in eating disorders (EDs) and self-induced vomiting (SV), a key symptom of different types of EDs. Perfectionism and impulsivity are potential risk factors for EDs. TPH2 (tryptophan hydroxylase 2) SNP rs1473473 was previously associated with anorexia nervosa and EDs characterized by SV. Could perfectionism or impulsivity be underlying the association between rs1473473 and EDs? Genetic association between TPH2 SNP rs1473473 and perfectionism or impulsivity was first evaluated in a random control group (N = 512). The associations obtained in this control group were subsequently tested in a group of patients with an ED (N = 267). The minor allele of rs1473473 (OR = 1.49) was more frequent in impulsive controls, but also in impulsive patients with an ED (OR = 1.83). The largest effect was found in the patients with an ED characterized by SV (OR = 2.51, p = 0.02). Genetic variation at the TPH2 gene appeared to affect impulsivity which, in turn, might predispose to the SV phenotype.

Twin specific risk factors in primary school achievements.

The main aim of this study was to examine twin specific risk factors that influence educational achievement in primary school. We included prenatal factors that are not unique to twins, except for zygosity, but show a higher prevalence in twins than in singletons. In addition, educational achievement was compared between twins and their nontwin siblings in a within-family design. Data were obtained from parents and teachers of approximately 10,000 twins and their nontwin siblings registered with the Netherlands Twin Register. Teachers rated the proficiency of the children on arithmetic, language, reading, and physical education, and reported a national educational achievement test score (CITO). Structural equation modeling showed that gestational age, birth weight, and sex were significant predictors of educational achievement, even after correction for socioeconomic status. Mode of delivery and zygosity did not have an effect, while parental age only influenced arithmetic. Mode of conception, incubator time, and birth complications negatively affected achievement in physical education. The comparison of educational achievement of twins and singletons showed significantly lower ratings on arithmetic, reading, and language in twins, compared to their older siblings, but not compared to their younger siblings. Low gestational age and low birth weight were the most important risk factors for lower educational achievement of twins in primary school. It seems that the differences observed between twins and their nontwin siblings in educational achievement can largely be explained by birth order within the family.

Influence of candidate genes on attention problems in children: a longitudinal study.

Attention problems form one of the core characteristics of Attention-Deficit Hyperactive Disorder (ADHD), a multifactorial neurodevelopmental disorder. From twin research it is clear that genes play a considerable role in the etiology and in the stability of ADHD in childhood. Association studies have focused on genes involved in the dopaminergic and serotoninergic systems, but with inconclusive results. This study investigated the effect of 26 Single Nucleotide Polymorphisms (SNPs) in genes encoding for serotonin receptors 2A (HTR2A), Catechol-O-Methyltransferase (COMT), Tryptophane Hydroxylase type 2 (TPH2), and Brain Derived Neurotrophic Factor (BDNF). Attention problems (AP) were assessed by parental report at ages 3, 7, 10, and 12 years in more than 16,000 twin pairs. There were 1148 genotyped children with AP data. We developed a longitudinal framework to test the genetic association effect. Based on all phenotypic data, a longitudinal model was formulated with one latent factor loading on all AP measures over time. The broad heritability for the AP latent factor was 82%, and the latent factor explained around 55% of the total phenotypic variance. The association of SNPs with AP was then modeled at the level of this factor. None of the SNPs showed a significant association with AP. The lowest p-value was found for the rs6265 SNP in the BDNF gene (p = 0.035). Overall, our results suggest no evidence for a role of these genes in childhood AP.

Genetic influences on handedness: data from 25,732 Australian and Dutch twin families.

Handedness refers to a consistent asymmetry in skill or preferential use between the hands and is related to lateralization within the brain of other functions such as language. Previous twin studies of handedness have yielded inconsistent results resulting from a general lack of statistical power to find significant effects. Here we present analyses from a large international collaborative study of handedness (assessed by writing/drawing or self report) in Australian and Dutch twins and their siblings (54,270 individuals from 25,732 families). Maximum likelihood analyses incorporating the effects of known covariates (sex, year of birth and birth weight) revealed no evidence of hormonal transfer, mirror imaging or twin specific effects. There were also no differences in prevalence between zygosity groups or between twins and their singleton siblings. Consistent with previous meta-analyses, additive genetic effects accounted for about a quarter (23.64%) of the variance (95%CI 20.17, 27.09%) with the remainder accounted for by non-shared environmental influences. The implications of these findings for handedness both as a primary phenotype and as a covariate in linkage and association analyses are discussed.

Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait.

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N=1316). Using both single-nucleotide polymorphism (SNP)- and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.

Can genetics help psychometrics? Improving dimensionality assessment through genetic factor modeling.

In the present article, we discuss the role that quantitative genetic methodology may play in assessing and understanding the dimensionality of psychological (psychometric) instruments. Specifically, we study the relationship between the observed covariance structures, on the one hand, and the underlying genetic and environmental influences giving rise to such structures, on the other. We note that this relationship may be such that it hampers obtaining a clear estimate of dimensionality using standard tools for dimensionality assessment alone. One situation in which dimensionality assessment may be impeded is that in which genetic and environmental influences, of which the observed covariance structure is a function, differ from each other in structure and dimensionality. We demonstrate that in such situations settling dimensionality issues may be problematic, and propose using quantitative genetic modeling to uncover the (possibly different) dimensionalities of the underlying genetic and environmental structures. We illustrate using simulations and an empirical example on childhood internalizing problems.

Effect of shared environmental factors on exercise behavior from age 7 to 12 years.

INTRODUCTION: The aim of this study was to investigate the relative influence of genetic and environmental factors on children's leisure time exercise behavior through the classic twin design. METHODS: Data were taken from The Netherlands Twin Register. The twins were 7 (n = 3966 subjects), 10 (n = 3562), and 12-yr-olds (n = 8687), with longitudinal data for 27% of the sample. Parents were asked to indicate the children's regular participation in leisure time exercise activities, including frequency and duration. Resemblance between monozygotic and dizygotic twins for weekly MET-hours spent on exercise activities was analyzed as a function of their genetic relatedness. RESULTS: Average weekly MET-hours increased with age for both boys (age 7 yr: 14.0 (SD = 11.8); age 10 yr: 22.6 (SD = 18.7); age 12 yr: 28.4 (SD = 24.9)) and girls (age 7 yr: 9.7 (SD = 9.5); age 10 yr: 15.3 (SD = 15.1); age 12 yr: 19.3 (SD = 19.8)). Around 13% of boys and girls across all age groups did not participate in any regular leisure time exercise activities. Tracking of exercise behavior from age 7 to 12 yr was modest (0.168 < r < 0.534). For boys, genetic effects accounted for 24% (confidence interval, 18%-30%) of the variance at age 7 yr, 66% (53%-81%) at age 10 yr, and 38% (32%-46%) at age 12 yr. For girls, this was 22% (15%-30%), 16% (9%-24%), and 36% (30%-43%), respectively. Environmental influences shared by children from the same family explained 71%, 25%, and 50% of the variance in boys (age 7, 10, and 12 yr) and 67%, 72%, and 53% in girls. The shared environment influencing exercise behavior was partially different between boys and girls. CONCLUSION: Our results stress the important role of shared environment for exercise behavior in young children.

A genetic study on attention problems and academic skills: results of a longitudinal study in twins.

OBJECTIVE: Several studies reported a negative association between ADHD symptoms and academic achievement. We investigated the etiology of the association between Attention Problems (AP, one of the core symptoms in ADHD) in early childhood and four academic skills across childhood in a genetically informative design. METHOD: Academic skills (mathematics, spelling, reading and comprehension) were measured with standardized tests performed at school in grade 2, 4, and 6. AP were measured with mother ratings of the Devereux Child Behavior Rating Scale at age 5 and the Child Behavior Checklist at age 7. Subjects were 767 Dutch twins from 445 families. RESULTS: AP were negatively associated with most academic skills in each grade, and this association was stable over time. Correlations of AP with mathematics and comprehension were around -0.20, and with spelling around -0.15. Correlations with reading were not significant. A significant genetic correlation (-0.40) between AP and mathematics across time indicated that shared genes play a role for these measures. The genetic correlations of AP with spelling and comprehension (both -0.28, p= 0.09) were non-significant. CONCLUSIONS: More complex academic skills, requiring higher cognitive processes, like mathematics and comprehension, are especially negatively associated with attention problems. The association between AP and mathematics is partly due to shared genes, while the association with comprehension, and spelling was driven by unique environmental factors.

Adolescent self-report of emotional and behavioral problems: interactions of genetic factors with sex and age.

OBJECTIVE: The aim of the current study was to investigate the sex and age effects on the mean levels and the genetic architecture of adolescent self-reported emotional and behavioral problems. METHOD: Survey data on psychopathology as assessed by the Youth Self Report (YSR; Achenbach & Rescorla, 2001) were collected in a large sample of Dutch adolescent twins and their non-twin siblings (6381 twins and 1195 siblings from 3511 families) aged 12 to 20 years. Sex and age effects on the levels of emotional and behavioral problems and on the genetic architecture were investigated using genetic structural equation modeling. RESULTS: For all syndrome scales of the YSR (except for Aggressive Behavior) and for the broadband scales Internalizing and Externalizing sex-differences in mean levels were found. Females score higher than males on Internalizing problems and its subscales (Anxious/Depressed and Withdrawn/Depressed), while males score higher than females on Externalizing behavior and its subscale Rule-Breaking. Age-effects on mean levels vary in strength and direction by syndrome and sex. An increase in problems with increasing age was seen for Anxiety/Depressed, while a decrease was observed for Somatic Complaints, Aggressive Behavior, and Social and Thought Problems. Significant genotype interactions with age and with sex were found for most scales of the YSR. These effects vary in strength and direction, resulting in differences in genetic architecture between males and females and developmental changes in genetic architecture throughout adolescence. For example the heritability for Anxious/Depressed and Withdrawn/Depressed behavior increases and the heritability of Externalizing behavior decreases throughout adolescence. CONCLUSIONS: Age and sex are found to be important moderators of both mean levels and the heritability of self-reported adolescent emotional and behavioral problems. Differences between adolescents in YSR syndrome and broadband scales are accounted for by genetic and non-shared environmental influences. We observed no influence of shared environment in this large sample. Clinical implications of the age and sex effects on the genetic architecture are discussed.