NTR

Infrastructure and User Services

VU and NTR invested heavily in good data stewardship for this national treasure, and an additional NWO Groot grant (480-15-001/674) allowed biomedical informatics specialists from the Hyve (https://thehyve.nl/) to create a state-of-the-art data repository based on open source software tailored to the NTR data. Intensive data management led to full annotation of quality controlled and harmonized variables in this repository. To enable collaborative data sharing with academic and non-academic partners, the NTR developed a controlled data access protocol to ensure adequate balancing of privacy protection under the EU’s General Data Protection Regulation (GDPR) and long-term accessibility of NTR data under FAIR (Findable, Accessible, Interoperable, Reusable) principles. A public Data Showcase allows researchers to explore and select NTR variables in a shopping cart (.JSON file) to be used in their data access requests. The underlying tranSMART database (‘NTR data repository’) enables data managers to rapidly convert these requests into user-ready data files spanning the molecular to phenotypic to social environmental levels. 

Internal and external researchers apply for these NTR datasets to be delivered through secure transfer protocols provided:

• they comply with medical-ethical standards and keep the research within the bounds of the informed consents,
• they are bona fide researchers embedded in a reputable research institute or organisation,
• they engage NTR collaborators when their research efforts conflicts with ongoing research obligations of NTR to its funders,
• the responsible official in their institute signs the NTR Data Sharing Agreement (with standard contractual clause for parties outside the EER).

Examples/description of the type of research

The classical twin study has been a powerful heuristic in behavioural, psychiatric and biomedical research for decades. It compares intra-pair trait resemblance between monozygotic (MZ) twins who share 100% of their DNA sequence and dizygotic (DZ) twins who share on average 50% of segregating genes. It was twin studies that demonstrated significant heritability for nearly all human traits, and they still remain the yard stick for estimating missing heritability in the current heyday of genome-wide association studies (GWAS). The NTR contains (rare) cases of discordant MZ twin pairs, who are genetically similar, yet discordant for a disease or complex trait. This is a unique and highly valuable group that allows assessment of associations between disease and changes in epigenetic and gene expression data, which is not confounded by DNA sequence variation. 

The NTR has seamlessly transitioned to the new molecular genetic era, where twin-family data bring even stronger research opportunities, and actively continuous to adapt and enrich ongoing data collection strategies with novel types of data (e.g. COVID pandemic-related) and novel types of data collection (e.g. ambulatory monitoring). By combining Mendelian randomization and ‘multi-omics’ data with the twin design, causal chains in complex systems can be discovered and effects of changes in one link of the chain on the next can be established with maximal control over confounding. Moderation of intervention effects by the individuals’ genome and (family) environment can be tested which is an essential prerequisite for successful application of ‘personalized medicine’. Finally, omics-enriched twin-family data allow the separation of genetic and cultural inheritance of behavioral and diseases traits, explaining the exact mechanisms by which these ‘run in the family’. The NTR reports back zygosity information based on DNA to twin families for free, which has high relevance to families and their care providers.
 

How to access the infrastructure

Controlled data access: External researchers, after consulting our data show case with all the metadata on the repository, apply for the NTR datasets to be delivered through secure transfer protocols provided:
Internal and external researchers apply for these NTR datasets to be delivered through secure transfer protocols provided:

• they comply with medical-ethical standards and keep the research within the bounds of the informed consents,
• they are bona fide researchers embedded in a reputable research institute or organisation,
• they engage NTR collaborators when their research efforts conflicts with ongoing research obligations of NTR to its funders,
• the responsible official in their institute signs the NTR Data Sharing Agreement (with standard contractual clause for parties outside the EER).