Polygenic Risk Scores in Neurodegenerative Diseases: a Review

This review summarizes the current state of the art of polygenic risk scores (PRSs) in the assessment of risk for neurodegenerative diseases. Polygenic risk scores have been used to identify the shared genetic architecture between comorbid complex traits, disease presentations, and disease endophenotypes. The pathological and symptomatologic overlap between neurodegenerative diseases is strikingly high. In some cases, the diagnostic decision is arbitrary depending on the first appearance of symptomatology. Genetic studies have demonstrated that the genetic architecture of each of these diseases is different, but has a high degree of overlap. The creation of polygenic risk scores has allowed a more accurate calculation of this overlap. However, the power of the PRS is dependent on the power of the genome-wide association studies (GWAS) used to describe the genetic architecture. Even though not all neurodegenerative disease GWAS have the same sample size, and thus the same power, the use of polygenic risk scores has been successful in demonstrating the genetic overlap that has been observed phenotypically.