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Project

Genetic neuro epidemiology.

Alzheimer's disease (AD) is an incapacitating, incurable disease characterized by a progressive loss of cognitive functions. It has a long disease course and ultimately requires fulltime medical care. Aside from drugs that temporarily relieve symptoms, no treatment exists for AD. More than 35 million people are living with dementia worldwide. With the growing proportion of people > 65 years, and the high costs associated with care for AD patients, the future impact of AD on society and public health is of great concern. Owing to technological progress and global collaborative research in the field of AD genetics, our understanding of the genetic foundations of AD is rapidly expanding. Genome-wide association studies (GWAS) have resulted in an explosion of new insights in the pathways underlying AD. At least twenty novel genetic risk loci have now been identified in addition to APOE ε4. GWAS have proven to be an excellent tool to locate new AD risk loci, but they are typically not sufficient to detect the actual risk variant(s) in the locus, let alone their downstream effects. Identification of the true risk alleles, however, is key in understanding the molecular mechanisms through which risk genes are involved in AD. Due to their location in a functional domain, or their mutation mechanism, these variants may shed light on the mechanism through which a gene is involved in AD, providing anchor points for downstream research. Epidemiological estimates of new risk genes, as well as genetic risk profiling become more precise once the true underlying genetic risk factors are known. The aim of this project is to discover these true genetic risk factors, using a well-characterized, longitudinal study cohort supported by a biobank holding a range of biomaterials, ascertained from a population characterized by large sibships and limited migration, creating founder effects that facilitate detection of otherwise rare genetic variants. We will make use of advanced genomic technologies, testing targeted hypotheses and integrating RNA sequencing. We will explore the clinical as well as scientific potential of genetic risk profiles for AD. We will investigate the clinical impact of rare variants of intermediate-to-high penetrance to evaluate if and how the knowledge of carrier status of such a variant can be used in genetic risk prediction and genetic subtyping, as a stepping-stone towards a precision medicine-based approach to AD care.
Date:1 Jan 2017 →  31 Dec 2021
Keywords:GENETICS, NEURODEGENERATIVE DISORDERS
Disciplines:Genetics, Systems biology, Molecular and cell biology, Public health care, Public health sciences, Public health services