Omics in Neurodegenerative Disease: Hope or Hype?

Maria Diaz-Ortiz et. al PDBP author: Alice S. Chen-Plotkin
Omics in Neurodegenerative Disease


The past 15 years have seen a boom in the use of ‘omic’ technologies to characterize Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration (FTLD). 

Genome-wide association studies (GWASs) in neurodegeneration have resulted in the characterization of >1 million individuals and the discovery of >100 disease-associated genetic risk loci. However, no targeted therapies (or late-phase clinical trials testing targeted therapies) have emerged from these studies and we expect diminishing returns from increasingly large GWASs. 

Functional investigation of TMEM106B, a genetic risk locus implicated by GWASs in FTLD, exemplifies a path from risk locus to target gene to biological pathway. 

Emphasis on the integration of knowledge into specific hypotheses that are then tested in cell-biological and animal-based model systems is needed.


The past 15 years have seen a boom in the use and integration of ‘omic’ approaches (limited here to genomic, transcriptomic, and epigenomic techniques) to study neurodegenerative disease in an unprecedented way. We first highlight advances in and the limitations of using such approaches in the neurodegenerative disease literature, with a focus on Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). We next discuss how these studies can advance human health in the form of generating leads for downstream mechanistic investigation or yielding polygenic risk scores (PRSs) for prognostication. However, we argue that these approaches constitute a new form of molecular description, analogous to clinical or pathological description, that alone does not hold the key to solving these complex diseases. 




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