Background
This study investigates the causal relationships between reading and print exposure and investigates whether the amount children read outside school determines how well they read, or vice ...versa. Previous findings from behavioural studies suggest that reading predicts print exposure. Here, we use twin‐data and apply the behaviour‐genetic approach of direction of causality modelling, suggested by Heath et al. (), to investigate the causal relationships between these two traits.
Method
Partial data were available for a large sample of twin children (N = 11,559) and 262 siblings, all enrolled in the Netherlands Twin Register. Children were assessed around 7.5 years of age. Mothers completed questionnaires reporting children's time spent on reading activities and reading ability. Additional information on reading ability was available through teacher ratings and performance on national reading tests. For siblings reading test, results were available.
Results
The reading ability of the twins was comparable to that of the siblings and national norms, showing that twin findings can be generalized to the population. A measurement model was specified with two latent variables, Reading Ability and Print Exposure, which correlated .41. Heritability analyses showed that Reading Ability was highly heritable, while genetic and environmental influences were equally important for Print Exposure. We exploited the fact that the two constructs differ in genetic architecture and fitted direction of causality models. The results supported a causal relationship running from Reading Ability to Print Exposure.
Conclusions
How much and how well children read are moderately correlated. Individual differences in print exposure are less heritable than individual differences in reading ability. Importantly, the present results suggest that it is the children's reading ability that determines how much they choose to read, rather than vice versa.
Background
Aggression in children has genetic and environmental causes. Studies of aggression can pool existing datasets to include more complex models of social effects. Such analyses require large ...datasets with harmonized outcome measures. Here, we made use of a reference panel for phenotype data to harmonize multiple aggression measures in school‐aged children to jointly analyze data from five large twin cohorts.
Methods
Individual level aggression data on 86,559 children (42,468 twin pairs) were available in five European twin cohorts measured by different instruments. A phenotypic reference panel was collected which enabled a model‐based phenotype harmonization approach. A bi‐factor integration model in the integrative data analysis framework was developed to model aggression across studies while adjusting for rater, age, and sex. Finally, harmonized aggression scores were analyzed to estimate contributions of genes, environment, and social interaction to aggression. The large sample size allowed adequate power to test for sibling interaction effects, with unique dynamics permitted for opposite‐sex twins.
Results
The best‐fitting model found a high level of overall heritability of aggression (~60%). Different heritability rates of aggression across sex were marginally significant, with heritability estimates in boys of ~64% and ~58% in girls. Sibling interaction effects were only significant in the opposite‐sex twin pairs: the interaction effect of males on their female co‐twin differed from the effect of females on their male co‐twin. An aggressive female had a positive effect on male co‐twin aggression, whereas more aggression in males had a negative influence on a female co‐twin.
Conclusions
Opposite‐sex twins displayed unique social dynamics of aggressive behaviors in a joint analysis of a large, multinational dataset. The integrative data analysis framework, applied in combination with a reference panel, has the potential to elucidate broad, generalizable results in the investigation of common psychological traits in children.
Low birth weight (LBW) is associated with attention problems (AP) and attention-deficit/hyperactivity disorder (ADHD). The etiology of this association is unclear. We investigate whether there is a ...causal influence of birth weight (BW) on AP and whether the BW effect is mediated by catch-up growth (CUG) in low-BW children.
Longitudinal data from >29,000 twins registered with the Netherlands Twin Register with BW ≥1,500 g and gestational age (GA) ≥32 weeks were analyzed with the cotwin control method. Hyperactivity and AP were assessed at ages 3, 7, 10, and 12 years; weight was assessed at birth and age 2 years.
Children in the lowest BW category of 1,500 to 2,000 g scored 0.18 to 0.37 standard deviations (SD) higher on AP than children in the reference category of 3,000 to 3,500 g. This effect was present in term-born and preterm-born children. Importantly, in BW discordant monozygotic (MZ), dizygotic (DZ), and unrelated (UR) pairs, the child with the lower BW scored higher on hyperactivity and AP than the child with the higher BW and within-pair differences were similar for MZ, DZ, and UR pairs. This pattern is consistent with a causal effect of BW on AP. MZ and DZ twin pairs concordant for LBW but discordant for CUG showed similar AP scores, thus ruling out any effect of CUG on AP.
These results strongly indicate that the association of birth weight and AP represents a causal relationship. The effects of BW are not explained by CUG in LBW children.
To review findings on attention-deficit/hyperactivity disorder and attention problems (AP) in children, adolescents, and adults, as established in the database of the Netherlands Twin Register and ...increase the understanding of stability in AP across the lifespan as a function of genetic and environmental influences.
A longitudinal model was fitted on Netherlands Twin Register AP scores from 44,607 child (<12-year-old), adolescent (12- to 18-year-old), and adult (>18-year-old) twins.
Mean AP showed a downward trend with age. Age-to-age correlations ranged from 0.33 (50-≥60 years old) to 0.73 (10-12 years old). Stability in individual differences in AP was due to genetic and environmental factors, and change was due primarily to environmental factors. Nonadditive genetic influences were present from childhood to adulthood. Total genetic variance decreased slightly throughout aging, whereas environmental variance increased substantially with the switch from maternal to self-ratings at 12 years of age. As a result, heritability coefficients decreased from 0.70 to 0.74 in childhood (maternal ratings) to 0.51 to 0.56 in adolescence (self-ratings), and 0.40 to 0.54 in adulthood (self-ratings). In childhood, male subjects scored higher than female subjects. After the rater switch at 12 years of age, female subjects tended to score higher than male subjects.
Stability of AP is the result of genetic and environmental stability. The decrease in estimated heritability at 12 years of age is due to an increase in occasion-specific environmental variance and likely reflects a methodologic effect. Because environmental influences have lasting effects on AP, their early detection is crucial.
The evolving field of multi‐omics combines data and provides methods for simultaneous analysis across several omics levels. Here, we integrated genomics (transmitted and non‐transmitted polygenic ...scores PGSs), epigenomics, and metabolomics data in a multi‐omics framework to identify biomarkers for Attention‐Deficit/Hyperactivity Disorder (ADHD) and investigated the connections among the three omics levels. We first trained single‐ and next multi‐omics models to differentiate between cases and controls in 596 twins (cases = 14.8%) from the Netherlands Twin Register (NTR) demonstrating reasonable in‐sample prediction through cross‐validation. The multi‐omics model selected 30 PGSs, 143 CpGs, and 90 metabolites. We confirmed previous associations of ADHD with glucocorticoid exposure and the transmembrane protein family TMEM, show that the DNA methylation of the MAD1L1 gene associated with ADHD has a relation with parental smoking behavior, and present novel findings including associations between indirect genetic effects and CpGs of the STAP2 gene. However, out‐of‐sample prediction in NTR participants (N = 258, cases = 14.3%) and in a clinical sample (N = 145, cases = 51%) did not perform well (range misclassification was 0.40, 0.57). The results highlighted connections between omics levels, with the strongest connections between non‐transmitted PGSs, CpGs, and amino acid levels and show that multi‐omics designs considering interrelated omics levels can help unravel the complex biology underlying ADHD.
Background
Whereas short and problematic sleep are associated with psychological problems in adolescence, causality remains to be elucidated. This study therefore utilized the discordant monozygotic ...cotwin design and cross‐lagged models to investigate how short and problematic sleep affect psychological functioning.
Methods
Adolescent twins (N = 12,803, 13–20 years, 42% male) completed questionnaires on sleep and psychological functioning repeatedly over a two‐year interval. Monozygotic twin pairs were classified as concordant or discordant for sleep duration and trouble sleeping. Resulting subgroups were compared regarding internalizing problems, externalizing problems, and subjective well‐being.
Results
Cross‐sectional analyses indicated associations of worse psychological functioning with both short sleep and problematic sleep, and cross‐lagged models indicate bidirectional associations. Longitudinal analyses showed that an increase in sleep problems experienced selectively by one individual of an identical twin pair was accompanied by an increase of 52% in internalizing problem scores and 25% in externalizing problem scores. These changes were significantly different from the within‐subject changes in cotwins with unchanged sleep quality (respectively, 3% increase and 5% decrease). Psychological functioning did, however, not worsen with decreasing sleep duration.
Conclusions
The findings suggest that sleep quality, rather than sleep duration, should be the primary target for prevention and intervention, with possible effect on psychological functioning in adolescents.
To examine the contributions of maternal and paternal age on offspring externalizing and internalizing problems, this study analyzed problem behaviors at age 10–12 years from four Dutch ...population‐based cohorts (N = 32,892) by a multiple informant design. Bayesian evidence synthesis was used to combine results across cohorts with 50% of the data analyzed for discovery and 50% for confirmation. There was evidence of a robust negative linear relation between parental age and externalizing problems as reported by parents. In teacher‐reports, this relation was largely explained by parental socio‐economic status. Parental age had limited to no association with internalizing problems. Thus, in this large population‐based study, either a beneficial or no effect of advanced parenthood on child problem behavior was observed.
Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount ...of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7-14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47-0.80) and lower with internalizing problems (r: 0.02-0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the higher mean levels of aggressive behavior in boys, the correlations were notably similar for boys and girls (e.g., aggressive-hyperactivity correlations: 0.51-0.75 boys, 0.47-0.70 girls) and did not vary greatly with respect to age, instrument or cohort. Thus, teacher-rated aggressive behavior rarely occurs in isolation; boys and girls with problems of aggressive behavior likely require help with other behavioral and emotional problems. Important to note, higher aggressive behavior is not only associated with higher amounts of other externalizing and internalizing problems but also with lower levels of prosocial behavior.
DNA methylation arrays are widely used in epigenome-wide association studies and methylation quantitative trait locus (mQTL) studies. Here, we performed the first genome-wide analysis of monozygotic ...(MZ) twin correlations and mQTLs on data obtained with the Illumina MethylationEPIC BeadChip (EPIC array) and compared the performance of the EPIC array to the Illumina HumanMethylation450 BeadChip (HM450 array) for buccal-derived DNA.
Good-quality EPIC data were obtained for 102 buccal-derived DNA samples from 49 MZ twin pairs (mean age = 7.5 years, range = 1-10). Differences between MZ twins in the cellular content of buccal swabs were a major driver for differences in their DNA methylation profiles, highlighting the importance to adjust for cellular composition in DNA methylation studies of buccal-derived DNA. After adjusting for cellular composition, the genome-wide mean correlation (r) between MZ twins was 0.21 for the EPIC array, and cis mQTL analysis in 84 twins identified 1,296,323 significant associations (FDR 5%), encompassing 33,749 methylation sites and 616,029 genetic variants. MZ twin correlations were slightly larger (p < 2.2 × 10
) for novel EPIC probes (N = 383,066, mean r = 0.22) compared to probes that are also present on HM450 (N = 406,822, mean r = 0.20). In line with this observation, a larger percentage of novel EPIC probes was associated with genetic variants (novel EPIC probes with significant mQTL 4.7%, HM450 probes with mQTL 3.9%, p < 2.2 × 10
). Methylation sites with a large MZ correlation and sites associated with mQTLs were most strongly enriched in epithelial cell DNase I hypersensitive sites (DHSs), enhancers, and histone mark H3K4me3.
We conclude that the contribution of familial factors to individual differences in DNA methylation and the effect of mQTLs are larger for novel EPIC probes, especially those within regulatory elements connected to active regions specific to the investigated tissue.