How the NND project helps the research community
The NBB has obtained brain material from over 4500 donors with a neurological or psychiatric diagnosis. Of the majority of these donors the NBB has also gained a vast amount of clinical information and postmortem neuropathological diagnosis made by expert neuropathologists stored in semi-structured clinical-pathological summaries.
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The Netherlands Neurogenetics Database integrates clinical, neuropathological and genetic data
In the NND project these qualitative data will be parsed and subjected to machine learning models to quantitatively describe a predefined set of clinical or neuropathological parameters, generating disease trajectories and neuropathological trait assessments. Genotype structure will be determined with the Global Screening Array and will be carried out at the Erasmus Medical Centre Human Genomics Facility for nearly 3000 donors. The information will be combined to compute Polygenic Risk Scores (PRS) for several Central Nervous System (CNS) disorders and traits, leading to new insights regarding the role of natural genetic variation on human brain diseases. We anticipate that we can look further than the standard neurological and psychiatric diagnoses and start to unravel patterns underlying subtypes within these diagnoses or symptoms that are comorbid between two or more disorders. This will further our ability to categorise CNS diseases into endophenotypes with their own underlying molecular pathways.
In addition, the NND project helps the NBB to expand its open access policy in order to allow the best use possible of the wealth of information that it holds. Currently, researchers can view and select some donor information via eNBB. Our view for the future is that this project will enable researchers not only to search more standardised donor and tissue characteristics with improved modules but also include genetic information for further analysis by the research community. We foresee that state of the art ‘multi-omics’ approaches can build on this database to investigate an array of expression profiles including gene and protein expression and epigenetics in the brain tissue of NBB donors. These novel lines of research will aid interpretation and unravel de mechanism of action of genetic variants identified by Genome-wide association studies (GWAS) associated with brain diseases.