The Evolution of Genetics: Alzheimer's and Parkinson's Diseases

Neuron. 2016 Jun 15;90(6):1154-1163. doi: 10.1016/j.neuron.2016.05.040.


Genetic discoveries underlie the majority of the current thinking in neurodegenerative disease. This work has been driven by the significant gains made in identifying causal mutations; however, the translation of genetic causes of disease into pathobiological understanding remains a challenge. The application of a second generation of genetics methods allows the dissection of moderate and mild genetic risk factors for disease. This requires new thinking in two key areas: what constitutes proof of pathogenicity, and how do we translate these findings to biological understanding. Here we describe the progress and ongoing evolution in genetics. We describe a view that rejects the tradition that genetic proof has to be absolute before functional characterization and centers on a multi-dimensional approach integrating genetics, reference data, and functional work. We also argue that these challenges cannot be efficiently met by traditional hypothesis-driven methods but that high content system-wide efforts are required.

Keywords: Alzheimer’s disease; Exome sequencing; Genetics; Genome-wide association; Parkinson’s disease.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alzheimer Disease / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genetics, Medical / trends*
  • Humans
  • Mutation
  • Parkinson Disease / genetics*
  • Research Design / trends