Systematic Assessment of Tandem Repeats in Alzheimer’s Disease (STaR-AD)

While genetics research in Alzheimer’s disease (AD) has made great leaps forward over the last two decades, much remains to be learned about the genetic forces driving an individual’s predisposition to the disease. We and others have completed a number of genome-wide association studies (GWAS) based on single nucleotide DNA sequence variants to delineate genes linked to AD risk. While these studies have, indeed, led to a substantial improvement in our understanding of AD genetics, a large portion (i.e., up to 50%) of the risk spectrum remains unexplained by these GWAS genes. A large part of this knowledge gap may be afforded by more complex genomic variants, so-called tandem repeats. These structures represent repetitive elements in the genome that are very widespread and have been identified as the genetic cause of several neurological disorders, e.g., Huntington’s disease. For a long time, comprehensively studying tandem repeats was hindered by technological limitations. Fortunately, with the development of next-generation sequencing methods, these limitations have now been overcome, allowing us to effectively and systematically study the role of tandem repeats in the genetic architecture of AD. If successful, the results of our study could provide essential new insights into disease mechanisms and serve as high-priority drug targets. Moreover, integration of tandem repeat data into personalized medicine approaches has the potential to substantially improve the precision of future AD risk prediction algorithms.