The Netherlands Twin Register (NTR) is a large nation-wide prospective cohort study in members of twin families (twins –or multiples-, siblings, parents, spouses and children of twins). In the past 30 years about 25% of all twins (from ~60.000 families) and a roughly equal number of their family members have taken part in research projects of the NTR. Participants filled out surveys across at least one, but most often multiple waves of data collection spaced 2 to 3 years apart. The NTR collects data in childhood and adolescence and in adulthood, with an increasing number of twins participating in all three of these life course phases. The childhood surveys focus on growth and physical development, wellbeing, health behaviors, and behavioral and emotional problems as rated by parents at ages 0, 3, 5, 7, 9/10 and 12 (ages 7, 9, 12 also by teachers). NTR surveys in adolescents (ages 12, 14 and 16) and adults (age ranges 18-97) address the general theme of individual differences in (risk factors for) mental and physical health (e.g. personality, marital status and family composition, educational and occupational level, religion, stressful life events, anxiety & depressive disorders, type 2 diabetes, cardiovascular disease). Based on zygosity and survey data, selected samples are invited for more deep phenotyping, e.g. assessing anthropometry, neurocognitive function, autonomic and central nervous system function (EEG/MRI), biomarkers (metabolomics, genome-wide methylation and gene expression, gut microbiome, telomere length), and cardiorespiratory fitness. Parallel biological sample collection has created a vast resource for future omics and biomarker studies: the NTR Biobank. Apart from inflammatory and cardiometabolic biomarkers, genome-wide genetic markers have been generated in blood and buccal samples collected in multiple projects, including a collaboration between VU and Avera Health Care, USA. Currently nearly 30,000 participants have been genotyped on genome-wide SNP arrays and ongoing DNA collection/GSA genotyping adds ~1500 genotypes per year. Uniquely, in over 20000 families NTR has genotyped multiple members in a family, which now turns out to be an asset in research into intergeneration transmission.
A majority of participants also consents to record linkage through anonymized procedures to external databases. Such linkage has been done for hospital collected data on placenta/chorion status of the twins (PALGA), irritable bowel disease (PALGA), and breast cancer (Cancer Registration). Record linkage can also be done in the CBS portal with health outcomes and health care use. Numerous databases in the Netherlands further allow for linkage to postal zone information, e.g. exposure to noise and air quality, and neighborhood characteristics.
Twin and family studies are paramount in understanding the genetic architecture of individual differences in complex human traits in the social, behavioral, and biomedical domains. The original question “are we the product of nature or nurture?” evolved into questions regarding the interplay of genetic variation with social and behavioral factors. NTR data allow sophisticated modeling of Genotype-Environment interaction and correlation, where genotype and environment are mutual moderators that are themselves subject to moderation by age, gender, birth cohort and culture. Understanding these dynamics can inform personalized interventions in the areas of schooling, lifestyle behaviors, cure and care, and numerous other targets that society holds to be important.
Combining longitudinal data on behavior, health and environmental exposures with the rich molecular genetic information in the NTR biobank moves research beyond the discovery of common genetic variants and pathways. We now see multi-omics opportunities being applied in within twin-family data as one of the most powerful research designs to tackle research questions on causality and prediction.