Intergenerational transmission of ADHD behaviors: genetic and environmental pathways.

BACKGROUND: We investigate if covariation between parental and child attention-deficit hyperactivity disorder (ADHD) behaviors can be explained by environmental and/or genetic transmission. METHODS: We employed a large children-of-twins-and-siblings sample (N = 22 276 parents and 11 566 8-year-old children) of the Norwegian Mother, Father and Child Cohort Study. This enabled us to disentangle intergenerational influences via parental genes and parental behaviors (i.e. genetic and environmental transmission, respectively). Fathers reported on their own symptoms and mothers on their own and their child's symptoms. RESULTS: Child ADHD behaviors correlated with their mother's (0.24) and father's (0.10) ADHD behaviors. These correlations were largely due to additive genetic transmission. Variation in children's ADHD behaviors was explained by genetic factors active in both generations (11%) and genetic factors specific to the children (46%), giving a total heritability of 57%. There were small effects of parental ADHD behaviors (2% environmental transmission) and gene-environment correlation (3%). The remaining variability in ADHD behaviors was due to individual-specific environmental factors. CONCLUSIONS: The intergenerational resemblance of ADHD behaviors is primarily due to genetic transmission, with little evidence for parental ADHD behaviors causing children's ADHD behaviors. This contradicts theories proposing environmental explanations of intergenerational transmission of ADHD, such as parenting theories or psychological life-history theory.

Are Genetic and Environmental Risk Factors for Psychopathology Amplified in Children with Below-Average Intelligence? A Population-Based Twin Study.

There is a negative association between intelligence and psychopathology. We analyzed data on intelligence and psychopathology to assess this association in seven-year-old Dutch twin pairs (ranging from 616 to 14,150 depending on the phenotype) and estimated the degree to which genetic and environmental factors common to intelligence and psychopathology explain the association. Secondly, we examined whether genetic and environmental effects on psychopathology are moderated by intelligence. We found that intelligence, as assessed by psychometric IQ tests, correlated negatively with childhood psychopathology, as assessed by the DSM-oriented scales of the Child Behavior Check List (CBCL). The correlations ranged between - .09 and - .15 and were mainly explained by common genetic factors. Intelligence moderated genetic and environmental effects on anxiety and negative affect, but not those on ADHD, ODD, and autism. The heritability of anxiety and negative affect was greatest in individuals with below-average intelligence. We discuss mechanisms through which this effect could arise, and we end with some recommendations for future research.

Literacy skills seem to fuel literacy enjoyment, rather than vice versa.

Children who like to read and write tend to be better at it. This association is typically interpreted as enjoyment impacting engagement in literacy activities, which boosts literacy skills. We fitted direction-of-causation models to partial data of 3690 Finnish twins aged 12. Literacy skills were rated by the twins' teachers and literacy enjoyment by the twins themselves. A bivariate twin model showed substantial genetic influences on literacy skills (70%) and literacy enjoyment (35%). In both skills and enjoyment, shared-environmental influences explained about 20% in each. The best-fitting direction-of-causation model showed that skills impacted enjoyment, while the influence in the other direction was zero. The genetic influences on skills influenced enjoyment, likely via the skills→enjoyment path. This indicates an active gene-environment correlation: children with an aptitude for good literacy skills are more likely to enjoy reading and seek out literacy activities. To a lesser extent, it was also the shared-environmental influences on children's skills that propagated to influence children's literacy enjoyment. Environmental influences that foster children's literacy skills (e.g., families and schools), also foster children's love for reading and writing. These findings underline the importance of nurturing children's literacy skills. HIGHLIGHTS: It's known that how much children enjoy reading and writing and how good they are at it correlates ∼0.30, but causality remains unknown. We tested the direction of causation in 3690 twins aged 12. Literacy skills impacted literacy enjoyment, but not the other way around. Genetics influence children's literacy skills and how much they like and choose to read and write, indicating genetic niche picking.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases  = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

Intergenerational Transmission of BMI and Educational Outcomes in Children and Adolescents.

Individual differences in educational attainment (EA) and physical health, as indexed by body mass index (BMI), are correlated within individuals and across generations. The aim of our study was to assess the transmission of these traits from parents to their offspring in childhood and adolescence. We analyzed BMI and EA in 13,916 families from the Netherlands. Data were available for 27,577 parents (mean age 33) and 26,855 of their offspring at 4 and 12 years of age. We employed structural equation modeling to simultaneously estimate the phenotypic transmission of BMI and EA from parents to offspring, the spousal correlations, and the residual child BMI-EA associations after accounting for intergenerational transmission and testing for gender differences therein. We found a significant intergenerational transmission of BMI to BMI in childhood (age 4; standardized regression coefficient ß = .10) and adolescence (age 12; ß = .20), and of EA to academic achievement in adolescence (ß = .19). Cross-trait parent-to-offspring transmission was weak. All transmission effects were independent of parent or offspring gender. We observed within-person EA-BMI correlations that were negative in parents (∼-.09), positive in children (∼.05) and negative in adolescents (∼-.06). Residual EA-BMI were positive in children (∼.05) and insignificant in adolescents. Spousal correlations were .46 for EA, .21 for BMI, and ∼-.09 cross-trait. After accounting for spousal correlations, the intergenerational transmission for BMI and EA is mainly predictive within, but not across, traits. The within-person correlation between BMI and EA can change in direction between childhood and adulthood.

Intergenerational transmission of body mass index and associations with educational attainment.

BACKGROUND: Individual differences in educational attainment (EA) and physical health, as indexed by body mass index (BMI), are correlated within persons and across generations. The present aim was to assess these associations while controlling for parental transmission. METHODS: We analyzed BMI and EA obtained for 8,866 families from the Netherlands. Data were available for 19,132 persons, including 6,901 parents (mean age 54) and 12,234 of their adult offspring (mean age 32). We employed structural equation modeling to simultaneously model the direct and indirect transmission of BMI and EA from parents to offspring, spousal correlations, and the residual within-person BMI-EA association and tested for gender differences in the transmission parameters. RESULTS: We found moderate intergeneration transmission for BMI (standardized beta ~ .20) and EA (~ .22), and substantial spousal correlations for BMI (.23) and EA (.51). Cross-trait parent to offspring transmission was weak. The strength of transmission was largely independent of parent or offspring gender. Negative within person EA-BMI correlations were observed for all family members (fathers, -0.102; mothers, -0.147; sons, -0.154; daughters, -0.173). About 60% of the EA-BMI correlation in offspring persisted after taking into account the intergeneration transmission. CONCLUSIONS: The intergenerational transmission for BMI and EA is mainly predictive within traits. Significant spousal and within person correlations in the parental generation are responsible for the effect of parental EA on offspring BMI. Offspring EA and BMI are further correlated beyond parental influences.

Multilevel Twin Models: Geographical Region as a Third Level Variable.

The classical twin model can be reparametrized as an equivalent multilevel model. The multilevel parameterization has underexplored advantages, such as the possibility to include higher-level clustering variables in which lower levels are nested. When this higher-level clustering is not modeled, its variance is captured by the common environmental variance component. In this paper we illustrate the application of a 3-level multilevel model to twin data by analyzing the regional clustering of 7-year-old children's height in the Netherlands. Our findings show that 1.8%, of the phenotypic variance in children's height is attributable to regional clustering, which is 7% of the variance explained by between-family or common environmental components. Since regional clustering may represent ancestry, we also investigate the effect of region after correcting for genetic principal components, in a subsample of participants with genome-wide SNP data. After correction, region no longer explained variation in height. Our results suggest that the phenotypic variance explained by region might represent ancestry effects on height.

Parental Age in Relation to Offspring's Neurodevelopment.

Objective: Advanced parenthood increases the risk of severe neurodevelopmental disorders like autism, Down syndrome and schizophrenia. Does advanced parenthood also negatively impact offspring's general neurodevelopment?Method: We analyzed child-, father-, mother- and teacher-rated attention-problems (N = 38,024), and standardized measures of intelligence (N = 10,273) and educational achievement (N = 17,522) of children from four Dutch population-based cohorts. The mean age over cohorts varied from 9.73-13.03. Most participants were of Dutch origin, ranging from 58.7%-96.7% over cohorts. We analyzed 50% of the data to generate hypotheses and the other 50% to evaluate support for these hypotheses. We aggregated the results over cohorts with Bayesian research synthesis.Results: We mostly found negative linear relations between parental age and attention-problems, meaning that offspring of younger parents tended to have more attention problems. Maternal age was positively and linearly related to offspring's IQ and educational achievement. Paternal age showed an attenuating positive relation with educational achievement and an inverted U-shape relation with IQ, with offspring of younger and older fathers at a disadvantage. Only the associations with maternal age remained after including SES. The inclusion of child gender in the model did not affect the relation between parental age and the study outcomes.Conclusions: Effects were small but significant, with better outcomes for children born to older parents. Older parents tended to be of higher SES. Indeed, the positive relation between parental age and offspring neurodevelopmental outcomes was partly confounded by SES.

Intergenerational Transmission of Education and ADHD: Effects of Parental Genotypes.

It remains a challenge to determine whether children resemble their parents due to nature, nurture, or a mixture of both. Here we used a design that exploits the distinction between transmitted and non-transmitted alleles in genetic transmission from parent to offspring. Two separate polygenic scores (PGS) were calculated on the basis of the transmitted and non-transmitted alleles. The effect of the non-transmitted PGS is necessarily mediated by parental phenotypes, insofar as they contribute to the rearing environment of the offspring (genetic nurturing). We calculated transmitted and non-transmitted PGSs associated with adult educational attainment (EA) and PGSs associated with childhood ADHD in a general population sample of trios, i.e. child or adult offspring and their parents (N = 1120-2518). We tested if the EA and ADHD (non-)transmitted PGSs were associated with childhood academic achievement and ADHD in offspring. Based on the earlier findings for shared environment, we hypothesized to find genetic nurturing for academic achievement, but not for ADHD. In adults, both transmitted (R2 = 7.6%) and non-transmitted (R2 = 1.7%) EA PGSs were associated with offspring EA, evidencing genetic nurturing. In children around age 12, academic achievement was associated with the transmitted EA PGSs (R2 = 5.7%), but we found no support for genetic nurturing (R2 ~ 0.1%). The ADHD PGSs were not significantly associated with academic achievement (R2 ~ 0.6%). ADHD symptoms in children were only associated with transmitted EA PGSs and ADHD PGSs (R2 = 1-2%). Based on these results, we conclude that the associations between parent characteristics and offspring outcomes in childhood are mainly to be attributable to the effects of genes that are shared by parents and children.

Unraveling the Relation Between Reading Comprehension and Print Exposure.

The purpose of this study was to test the directionality of influence between reading comprehension (RC) and print exposure (PE), thereby estimating genetic and environmental effects of this relation. The sample consisted of 910 twins in fourth through ninth grades (Mage  = 12.33 years, SD = 1.41) from the Florida Twin Project on Reading, Behavior, and Environment. Using direction-of-causation model in a twin design, results supported a direction of influence running from RC to PE. This relation was underpinned by genetic and environmental factors of RC as well as PE. Implications for reading education are discussed.

Genetic and Environmental Influences on Different Forms of Bullying Perpetration, Bullying Victimization, and Their Co-occurrence.

Bullying comes in different forms, yet most previous genetically-sensitive studies have not distinguished between them. Given the serious consequences and the high prevalence of bullying, it is remarkable that the aetiology of bullying and its different forms has been under-researched. We present the first study to investigate the genetic architecture of bullying perpetration, bullying victimization, and their co-occurrence for verbal, physical and relational bullying. Primary-school teachers rated 8215 twin children on bullying perpetration and bullying victimization. For each form of bullying, we investigated, through genetic structural equation modelling, the genetic and environmental influences on being a bully, a victim or both. 34% of the children were involved as bully, victim, or both. The correlation between being a bully and being a victim varied from 0.59 (relational) to 0.85 (physical). Heritability was ~ 70% for perpetration and ~ 65% for victimization, similar in girls and boys, yet both were somewhat lower for the relational form. Shared environmental influences were modest and more pronounced among girls. The correlation between being a bully and being a victim was explained mostly by genetic factors for verbal (~ 71%) and especially physical (~ 77%) and mostly by environmental factors for relational perpetration and victimization (~ 60%). Genes play a large role in explaining which children are at high risk of being a victim, bully, or both. For victimization this suggests an evocative gene-environment correlation: some children are at risk of being exposed to bullying, partly due to genetically influenced traits. So, genetic influences make some children more vulnerable to become a bully, victim or both.

The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs.

The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources - the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping - allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.

Why do children read more? The influence of reading ability on voluntary reading practices.

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.

Bullying and Victimization: The Effect of Close Companionship.

Peer bullying and victimization are a widespread phenomenon among school-age children and can have detrimental effects on the development of children. To examine whether having a close companion during childhood increases or decreases risk of victimization and bullying, this study compared twins to singleton children. A large group of twins (n = 9,909) were included who were compared to their related non-twin siblings (n = 1,534) aged 7-12 from the Netherlands Twin Register, thus creating optimal matching between twins and non-twins. Bullying and victimization were each based on a four-item scale filled out by their teachers. Prevalence rates for either bullying or victimization did not differ between twins and singletons. In total, in the past couple of months, 36% of children bullied peers moderately to severely, and 35% suffered moderately to severely from victimization. Boys were more likely to bully and were more prone to becoming a victim than girls. The most notable finding is that female twin pairs placed together in the same classroom did not bully more often, but were victimized less often, thus pointing to a protective effect of having a close companion in the classroom.

No Evidence of Causal Effects of Blood Pressure on Cognition in the Population at Large.

The large body of literature on the association between blood pressure (BP) and cognitive functioning has yielded mixed results, possibly due to the presence of non-linear effects across age, or because BP affects specific brain areas differently, impacting more on some cognitive skills than on others. If a robust association was detected among BP and specific cognitive tasks, the causal nature of reported associations between BP and cognition could be investigated in twin data, which allow a test of alternative explanations, including genetic pleiotropy. The present study first examines the association between BP and cognition in a sample of 1,140 participants with an age range between 10 and 86 years. Linear and quadratic effects of systolic BP (SBP) and diastolic BP (DBP) on cognitive functioning were examined for 17 tests across five functions. Associations were corrected for effects of sex and linear and quadratic effects of age. Second, to test a causal model, data from 123 monozygotic (MZ) twin pairs were analyzed to test whether cognitive functioning of the twins with the higher BP was different from that of the co-twins with lower BP. Associations between BP and cognitive functioning were absent for the majority of the cognitive tests, with the exception of a lower speed of emotion identification and verbal reasoning in subjects with high diastolic BP. In the MZ twin pair analyses, no effects of BP on cognition were found. We conclude that in the population at large, BP level is not associated with cognitive functioning in a clinically meaningful way.

Underlying skills of oral and silent reading.

Many studies have examined reading and reading development. The majority of these studies, however, focused on oral reading rather than on the more dominant silent reading mode. Similarly, it is common practice to assess oral reading abilities rather than silent reading abilities in schools and in diagnosis of reading impairments. More important, insights gained through examinations of oral reading tend to be generalized to silent reading. In the current study, we examined whether such generalizations are justified. We directly compared oral and silent reading fluency by examining whether these reading modes relate to the same underlying skills. In total, 132 fourth graders read words, sentences, and text orally, and 123 classmates read the same material silently. As underlying skills, we considered phonological awareness, rapid naming, and visual attention span. All skills correlated significantly with both reading modes. Phonological awareness contributed equally to oral and silent reading. Rapid naming, however, correlated more strongly with oral reading than with silent reading. Visual attention span correlated equally strongly with both reading modes but showed a significant unique contribution only to silent reading. In short, we showed that oral and silent reading indeed are fairly similar reading modes, based on the relations with reading-related cognitive skills. However, we also found differences that warrant caution in generalizing findings across reading modes.

Evaluating the causal relationship between educational attainment and mental health.

We investigate the causal relationship between educational attainment (EA) and mental health using two research designs. First, we compare the relationship between EA and 18 psychiatric diagnoses within sibship in Dutch national registry data (N=1.7 million), thereby controlling for unmeasured familial factors. Second, we apply two-sample Mendelian Randomization, which uses genetic variants related to EA or psychiatric diagnosis as instrumental variables, to test whether there is a causal relation in either direction. Our results suggest that lower levels of EA causally increase the risk of MDD, ADHD, alcohol dependence, GAD and PTSD diagnoses. We also find evidence of a causal effect of ADHD on EA. For schizophrenia, anorexia nervosa, OCD, and bipolar disorder, results were inconsistent across the different approaches, highlighting the importance of using multiple research designs to understand complex relationships such as between EA and mental health.

More than nature and nurture, indirect genetic effects on children's academic achievement are consequences of dynastic social processes.

Families transmit genes and environments across generations. When parents' genetics affect their children's environments, these two modes of inheritance can produce an 'indirect genetic effect'. Such indirect genetic effects may account for up to half of the estimated genetic variance in educational attainment. Here we tested if indirect genetic effects reflect within-nuclear-family transmission ('genetic nurture') or instead a multi-generational process of social stratification ('dynastic effects'). We analysed indirect genetic effects on children's academic achievement in their fifth to ninth years of schooling in N = 37,117 parent-offspring trios in the Norwegian Mother, Father, and Child Cohort Study (MoBa). We used pairs of genetically related families (parents were siblings, children were cousins; N = 10,913) to distinguish within-nuclear-family genetic-nurture effects from dynastic effects shared by cousins in different nuclear families. We found that indirect genetic effects on children's academic achievement cannot be explained by processes that operate exclusively within the nuclear family.

Dissociating crossmodal and verbal demands in paired associate learning (PAL): what drives the PAL-reading relationship?

Recent research suggests that visual-verbal paired associate learning (PAL) may tap a crossmodal associative learning mechanism that plays a distinct role in reading development. However, evidence from children with dyslexia indicates that deficits in visual-verbal PAL are strongly linked to the verbal demands of the task. The primary aim of this study was to disassociate the role of modality and verbal demand in driving the PAL-reading relationship. To do so, we compared performance across four PAL mapping conditions: visual-verbal, verbal-verbal, visual-visual and verbal-visual. We reasoned that if crossmodal mapping demand accounts for the PAL-reading relationship, both visual-verbal PAL and verbal-visual PAL should exhibit significant relationships with reading ability. The results were incompatible with the crossmodal hypothesis. Only tasks requiring verbal output (visual-verbal PAL and verbal-verbal PAL) significantly correlated with reading ability. In addition, visual-verbal PAL and verbal-verbal PAL were well represented by a latent "verbal output PAL" factor. Structural equation modeling showed that this factor fully accounted for the PAL-reading relationship; visual-verbal PAL did not add anything to the prediction of reading above and beyond this latent factor. The results are interpreted according to an alternative verbal account of the PAL-reading relationship.

Precursors of developmental dyslexia: an overview of the longitudinal Dutch Dyslexia Programme study.

Converging evidence suggests that developmental dyslexia is a neurobiological disorder, characterized by deficits in the auditory, visual, and linguistic domains. In the longitudinal project of the Dutch Dyslexia Programme, 180 children with a familial risk of dyslexia (FR) and a comparison group of 120 children without FR (noFR) were followed from the age of 2 months up to 9 years. Children were assessed on (1) auditory, speech, and visual event-related potentials every half year between 2 and 41 months; (2) expressive and receptive language, motor development, behaviour problems, and home-literacy environment by questionnaires at the age of 2 and 3; (3) speech-language and cognitive development from 47 months onwards; and (4) preliteracy and subskills of reading, and reading development during kindergarten and Grades 2 and 3. With regard to precursors of reading disability, first analyses showed specific differences between FR and noFR children in neurophysiological, cognitive, and early language measures. Once reading tests administered from age 7 to 9 years were available, the children were divided into three groups: FR children with and without dyslexia, and controls. Analyses of the differences between reading groups yielded distinct profiles and developmental trajectories. On early speech and visual processing, and several cognitive measures, performance of the non-dyslexic FR group differed from the dyslexic FR group and controls, indicating continuity of the influence of familial risk. Parental reading and rapid naming skills appeared to indicate their offspring's degree of familial risk. Furthermore, on rapid naming and nonverbal IQ, the non-dyslexic FR group performed similarly to the controls, suggesting protective factors. There are indications of differences between the FR and control groups, irrespective of reading outcome. These results contribute to the distinction between the deficits correlated to dyslexia as a manifest reading disorder and deficits correlated to familial risk only.