Genetic Risk Profiling in Parkinson's Disease and Utilizing Genetics to Gain Insight into Disease-Related Biological Pathways.

Abstract

Parkinson's disease (PD) is a complex disorder underpinned by both environmental and genetic factors. The latter only began to be understood around two decades ago, but since then great inroads have rapidly been made into deconvoluting the genetic component of PD. In particular, recent large-scale projects such as genome-wide association (GWA) studies have provided insight into the genetic risk factors associated with genetically ''complex'' PD (PD that cannot readily be attributed to single deleterious mutations). Here, we discuss the plethora of genetic information provided by PD GWA studies and how this may be utilized to generate polygenic risk scores (PRS), which may be used in the prediction of risk and trajectory of PD. We also comment on how pathway-specific genetic profiling can be used to gain insight into PD-related biological pathways, and how this may be further utilized to nominate causal PD genes and potentially druggable therapeutic targets. Finally, we outline the current limits of our understanding of PD genetics and the potential contribution of variation currently uncaptured in genetic studies, focusing here on uncatalogued structural variants.

• Authors: Ashley Hall, Sara Bandres-Ciga, Monica Diez-Fairen, John P Quinn, Kimberley J Billingsley
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 19 (Oct 04 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33020390 (Publication Type: Journal Article, Review)

Topics

• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Parkinson Disease (genetics, pathology)
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Signal Transduction (genetics)