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 resourcesthe longitudinal phenotyping, the extended pedigree structures and the multigeneration genotypingallow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.

The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.

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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 behaviourgenetic approach of direction of causality modelling, suggested by Heath et al. (1993), 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.

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 (R 2 = 7.6%) and non-transmitted (R 2 = 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 (R 2 = 5.7%), but we found no support for genetic nurturing (R 2 ~ 0.1%). The ADHD PGSs were not significantly associated with academic achievement (R 2 ~ 0.6%). ADHD symptoms in children were only associated with transmitted EA PGSs and ADHD PGSs (R 2 = 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.

The results of this study appear to support the hypothesis that individuals with increased genetic risk tend to live in urban/dense areas and suggest the need to refine the social stress model for schizophrenia by including genetics as well as possible gene-environment interactions.

This study used a theoretically-derived set of items of the Achenbach System of Empirically Based Assessment to develop the Achenbach Self-Control Scale (ASCS) for 7–16 year olds. Using a large dataset of over 20,000 children, who are enrolled in the Netherlands Twin Register, we demonstrated the psychometric properties of the ASCS for parent-, self- and teacher-report by examining internal and criterion validity, and inter-rater and test–retest reliability. We found associations between the ASCS and measures of well-being, educational achievement, and substance use. Next, we applied the classical twin design to estimate the genetic and environmental contributions to self-control. Genetic influences accounted for 64–75% of the variance in self-control based on parent- and teacher-report (age 7–12), and for 47–49% of the variance in self-control based on self-report (age 12–16), with the remaining variance accounted by non-shared environmental influences. In conclusion, we developed a validated and accessible self-control scale, and show that genetic influences explain a majority of the individual differences in self-control across youth aged 7–16 years.Electronic supplementary materialThe online version of this article (10.1007/s10519-018-9887-1) contains supplementary material, which is available to authorized users.

The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA metaanalysis of educational attainment in adults were used to calculate polygenic scores in an independent sample of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale.