Format

Send to

Choose Destination
Cell Tissue Res. 2018 Jul;373(1):9-20. doi: 10.1007/s00441-018-2817-y. Epub 2018 Mar 13.

Genetic risk factors in Parkinson's disease.

Author information

1
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD, 20892, USA.
2
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3BX, Liverpool, UK.
3
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD, 20892, USA. singleta@mail.nih.gov.

Abstract

Over the last two decades, we have witnessed a revolution in the field of Parkinson's disease (PD) genetics. Great advances have been made in identifying many loci that confer a risk for PD, which has subsequently led to an improved understanding of the molecular pathways involved in disease pathogenesis. Despite this success, it is predicted that only a relatively small proportion of the phenotypic variability has been explained by genetics. Therefore, it is clear that common heritable components of disease are still to be identified. Dissecting the genetic architecture of PD constitutes a critical effort in identifying therapeutic targets and although such substantial progress has helped us to better understand disease mechanism, the route to PD disease-modifying drugs is a lengthy one. In this review, we give an overview of the known genetic risk factors in PD, focusing not on individual variants but the larger networks that have been implicated following comprehensive pathway analysis. We outline the challenges faced in the translation of risk loci to pathobiological relevance and illustrate the need for integrating big-data by noting success in recent work which adopts a broad-scale screening approach. Lastly, with PD genetics now progressing from identifying risk to predicting disease, we review how these models will likely have a significant impact in the future.

KEYWORDS:

Common risk factors; Genetics; Genome-wide association study; Parkinson’s disease; Prediction

PMID:
29536161
PMCID:
PMC6201690
DOI:
10.1007/s00441-018-2817-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center