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There are research questions whose answers require record linkage of multiple databases that may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study on expenditure for total health, mental health, primary and hospital care, and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.
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.
A literature review was carried out to identify pre and perinatal characteristics associated with variation in Apgar scores in population-based studies. The parameters identified in the literature search were included in the classical twin design study to estimate effects of pre and perinatal factors shared and nonshared by twins and to test for a contribution of genetic factors in 1- and 5-min Apgar scores in a large sample of Dutch monozygotic (MZ) and dizygotic (DZ) twins. The sample included MZ and DZ twins (N = 5181 pairs) recruited by the Netherlands Twin Register shortly after birth, with data on prenatal characteristics and Apgar scores at first and/or fifth minutes. The ordinal regression and structural equation modeling were used to analyze the effects of characteristics identified in the literature review and to estimate genetic and nongenetic variance components. The literature review identified 63 papers. Consistent with the review, we observed statistically significant effects of birth order, zygosity and gestational age (GA) for 1- and 5-min Apgar scores of both twins. Apgar scores are higher in first-born versus second-born twins and DZ first-born versus MZ first-born twins. Birth weight had an effect on the 5-min Apgar of the first born. Fetal presentation and mode of delivery had different effects on Apgar scores of first- and second-born twins. Parental characteristics and chorionicity did not have significant main effects on Apgar scores. The MZ twins’ Apgar correlations equaled the DZ Apgar correlations. Our analyses suggest that individual differences in 1- and 5-min Apgar scores are attributable to shared and nonshared pre and perinatal factors, but not to genotypic factors of the newborns. The main predictors of Apgar scores are birth order, zygosity, GA, birth weight, mode of delivery and fetal presentation.
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.
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.
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.
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